diff --git a/src/file.ts b/src/file.ts
index 1237fd01d4..9847239603 100644
--- a/src/file.ts
+++ b/src/file.ts
@@ -31,7 +31,14 @@ import * as extend from 'extend';
 import * as fs from 'fs';
 import * as mime from 'mime';
 import * as resumableUpload from './resumable-upload';
-import {Writable, Readable, pipeline, Transform, PassThrough} from 'stream';
+import {
+  Writable,
+  Readable,
+  pipeline,
+  Transform,
+  PassThrough,
+  PipelineSource,
+} from 'stream';
 import * as zlib from 'zlib';
 import * as http from 'http';
 
@@ -93,6 +100,8 @@ export interface PolicyDocument {
   signature: string;
 }
 
+export type SaveData = string | Buffer | PipelineSource<string | Buffer>;
+
 export type GenerateSignedPostPolicyV2Response = [PolicyDocument];
 
 export interface GenerateSignedPostPolicyV2Callback {
@@ -419,6 +428,7 @@ export enum FileExceptionMessages {
   UPLOAD_MISMATCH = `The uploaded data did not match the data from the server.
     As a precaution, the file has been deleted.
     To be sure the content is the same, you should try uploading the file again.`,
+  STREAM_NOT_READABLE = 'Stream must be readable.',
 }
 
 /**
@@ -3527,13 +3537,9 @@ class File extends ServiceObject<File> {
     this.copy(newFile, copyOptions, callback!);
   }
 
-  save(data: string | Buffer, options?: SaveOptions): Promise<void>;
-  save(data: string | Buffer, callback: SaveCallback): void;
-  save(
-    data: string | Buffer,
-    options: SaveOptions,
-    callback: SaveCallback
-  ): void;
+  save(data: SaveData, options?: SaveOptions): Promise<void>;
+  save(data: SaveData, callback: SaveCallback): void;
+  save(data: SaveData, options: SaveOptions, callback: SaveCallback): void;
   /**
    * @typedef {object} SaveOptions
    * @extends CreateWriteStreamOptions
@@ -3560,7 +3566,7 @@ class File extends ServiceObject<File> {
    * resumable feature is disabled.
    * </p>
    *
-   * @param {string | Buffer} data The data to write to a file.
+   * @param {SaveData} data The data to write to a file.
    * @param {SaveOptions} [options] See {@link File#createWriteStream}'s `options`
    *     parameter.
    * @param {SaveCallback} [callback] Callback function.
@@ -3588,7 +3594,7 @@ class File extends ServiceObject<File> {
    * ```
    */
   save(
-    data: string | Buffer,
+    data: SaveData,
     optionsOrCallback?: SaveOptions | SaveCallback,
     callback?: SaveCallback
   ): Promise<void> | void {
@@ -3608,28 +3614,60 @@ class File extends ServiceObject<File> {
     }
     const returnValue = retry(
       async (bail: (err: Error) => void) => {
-        await new Promise<void>((resolve, reject) => {
+        if (data instanceof Readable && !data.readable) {
+          // Readable streams can only be consumed once and would cause a dead
+          // lock when used with pipeline().
+          return bail(new Error(FileExceptionMessages.STREAM_NOT_READABLE));
+        }
+
+        return new Promise<void>((resolve, reject) => {
           if (maxRetries === 0) {
             this.storage.retryOptions.autoRetry = false;
           }
-          const writable = this.createWriteStream(options)
-            .on('error', err => {
-              if (
-                this.storage.retryOptions.autoRetry &&
-                this.storage.retryOptions.retryableErrorFn!(err)
-              ) {
-                return reject(err);
+          const writable = this.createWriteStream(options);
+
+          if (options.onUploadProgress) {
+            writable.on('progress', options.onUploadProgress);
+          }
+
+          const handleError = (err: Error) => {
+            if (
+              !this.storage.retryOptions.autoRetry ||
+              !this.storage.retryOptions.retryableErrorFn!(err)
+            ) {
+              bail(err);
+            }
+
+            reject(err);
+          };
+
+          if (typeof data === 'string' || Buffer.isBuffer(data)) {
+            writable
+              .on('error', handleError)
+              .on('finish', () => resolve())
+              .end(data);
+          } else {
+            pipeline(data, writable, err => {
+              if (err) {
+                // If data is not a valid PipelineSource, then pipeline will
+                // fail without destroying the writable stream. If data is a
+                // PipelineSource that yields invalid chunks (e.g. a stream in
+                // object mode or an iterable that does not yield Buffers or
+                // strings), then pipeline will destroy the writable stream.
+                if (!writable.destroyed) writable.destroy();
+
+                if (typeof data !== 'function') {
+                  // Only PipelineSourceFunction can be retried. Async-iterables
+                  // and Readable streams can only be consumed once.
+                  bail(err);
+                }
+
+                handleError(err);
               } else {
-                return bail(err);
+                resolve();
               }
-            })
-            .on('finish', () => {
-              return resolve();
             });
-          if (options.onUploadProgress) {
-            writable.on('progress', options.onUploadProgress);
           }
-          writable.end(data);
         });
       },
       {
diff --git a/test/file.ts b/test/file.ts
index 14b493f229..27532953b5 100644
--- a/test/file.ts
+++ b/test/file.ts
@@ -4314,6 +4314,197 @@ describe('File', () => {
         await file.save(DATA, options, assert.ifError);
       });
 
+      it('should save a Readable with no errors', done => {
+        const options = {resumable: false};
+        file.createWriteStream = () => {
+          const writeStream = new PassThrough();
+          writeStream.on('data', data => {
+            assert.strictEqual(data.toString(), DATA);
+          });
+          writeStream.once('finish', done);
+          return writeStream;
+        };
+
+        const readable = new Readable({
+          read() {
+            this.push(DATA);
+            this.push(null);
+          },
+        });
+
+        void file.save(readable, options);
+      });
+
+      it('should propagate Readable errors', done => {
+        const options = {resumable: false};
+        file.createWriteStream = () => {
+          const writeStream = new PassThrough();
+          let errorCalled = false;
+          writeStream.on('data', data => {
+            assert.strictEqual(data.toString(), DATA);
+          });
+          writeStream.on('error', err => {
+            errorCalled = true;
+            assert.strictEqual(err.message, 'Error!');
+          });
+          writeStream.on('finish', () => {
+            assert.ok(errorCalled);
+          });
+          return writeStream;
+        };
+
+        const readable = new Readable({
+          read() {
+            setTimeout(() => {
+              this.push(DATA);
+              this.destroy(new Error('Error!'));
+            }, 50);
+          },
+        });
+
+        file.save(readable, options, (err: Error) => {
+          assert.strictEqual(err.message, 'Error!');
+          done();
+        });
+      });
+
+      it('Readable upload should not retry', async () => {
+        const options = {resumable: false};
+
+        let retryCount = 0;
+
+        file.createWriteStream = () => {
+          retryCount++;
+          return new Transform({
+            transform(
+              chunk: string | Buffer,
+              _encoding: string,
+              done: Function
+            ) {
+              this.push(chunk);
+              setTimeout(() => {
+                done(new HTTPError('retryable error', 408));
+              }, 5);
+            },
+          });
+        };
+        try {
+          const readable = new Readable({
+            read() {
+              this.push(DATA);
+              this.push(null);
+            },
+          });
+
+          await file.save(readable, options);
+          throw Error('unreachable');
+        } catch (e) {
+          assert.strictEqual((e as Error).message, 'retryable error');
+          assert.ok(retryCount === 1);
+        }
+      });
+
+      it('Destroyed Readable upload should throw', async () => {
+        const options = {resumable: false};
+
+        file.createWriteStream = () => {
+          throw new Error('unreachable');
+        };
+        try {
+          const readable = new Readable({
+            read() {
+              this.push(DATA);
+              this.push(null);
+            },
+          });
+
+          readable.destroy();
+
+          await file.save(readable, options);
+        } catch (e) {
+          assert.strictEqual(
+            (e as Error).message,
+            FileExceptionMessages.STREAM_NOT_READABLE
+          );
+        }
+      });
+
+      it('should save a generator with no error', done => {
+        const options = {resumable: false};
+        file.createWriteStream = () => {
+          const writeStream = new PassThrough();
+          writeStream.on('data', data => {
+            assert.strictEqual(data.toString(), DATA);
+            done();
+          });
+          return writeStream;
+        };
+
+        const generator = async function* (arg?: {signal?: AbortSignal}) {
+          await new Promise(resolve => setTimeout(resolve, 5));
+          if (arg?.signal?.aborted) return;
+          yield DATA;
+        };
+
+        void file.save(generator, options);
+      });
+
+      it('should propagate async iterable errors', done => {
+        const options = {resumable: false};
+        file.createWriteStream = () => {
+          const writeStream = new PassThrough();
+          let errorCalled = false;
+          writeStream.on('data', data => {
+            assert.strictEqual(data.toString(), DATA);
+          });
+          writeStream.on('error', err => {
+            errorCalled = true;
+            assert.strictEqual(err.message, 'Error!');
+          });
+          writeStream.on('finish', () => {
+            assert.ok(errorCalled);
+          });
+          return writeStream;
+        };
+
+        const generator = async function* () {
+          yield DATA;
+          throw new Error('Error!');
+        };
+
+        file.save(generator(), options, (err: Error) => {
+          assert.strictEqual(err.message, 'Error!');
+          done();
+        });
+      });
+
+      it('should error on invalid async iterator data', done => {
+        const options = {resumable: false};
+        file.createWriteStream = () => {
+          const writeStream = new PassThrough();
+          let errorCalled = false;
+          writeStream.on('error', () => {
+            errorCalled = true;
+          });
+          writeStream.on('finish', () => {
+            assert.ok(errorCalled);
+          });
+          return writeStream;
+        };
+
+        const generator = async function* () {
+          yield {thisIsNot: 'a buffer or a string'};
+        };
+
+        file.save(generator(), options, (err: Error) => {
+          assert.strictEqual(
+            err.message,
+            'The "chunk" argument must be of type string or an instance of Buffer or Uint8Array. Received an instance of Object'
+          );
+          done();
+        });
+      });
+
       it('buffer upload should retry on first failure', async () => {
         const options = {
           resumable: false,