diff --git a/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/pom.xml b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/pom.xml
index bac406ccdbc1c..3807caaaff689 100644
--- a/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/pom.xml
+++ b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/pom.xml
@@ -99,6 +99,11 @@
             <artifactId>quarkus-jaxrs-client-reactive-deployment</artifactId>
             <scope>test</scope>
         </dependency>
+        <dependency>
+            <groupId>io.quarkus</groupId>
+            <artifactId>quarkus-reactive-routes-deployment</artifactId>
+            <scope>test</scope>
+        </dependency>
     </dependencies>
 
     <build>
diff --git a/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/test/java/io/quarkus/resteasy/reactive/server/test/headers/VertxHeadersTest.java b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/test/java/io/quarkus/resteasy/reactive/server/test/headers/VertxHeadersTest.java
new file mode 100644
index 0000000000000..c2b902c7e2d50
--- /dev/null
+++ b/extensions/resteasy-reactive/quarkus-resteasy-reactive/deployment/src/test/java/io/quarkus/resteasy/reactive/server/test/headers/VertxHeadersTest.java
@@ -0,0 +1,63 @@
+package io.quarkus.resteasy.reactive.server.test.headers;
+
+import static io.restassured.RestAssured.when;
+import static org.assertj.core.api.Assertions.assertThat;
+
+import java.io.IOException;
+
+import javax.ws.rs.GET;
+import javax.ws.rs.Path;
+import javax.ws.rs.container.ContainerRequestContext;
+import javax.ws.rs.container.ContainerResponseContext;
+import javax.ws.rs.container.ContainerResponseFilter;
+import javax.ws.rs.core.HttpHeaders;
+import javax.ws.rs.ext.Provider;
+
+import org.junit.jupiter.api.Test;
+import org.junit.jupiter.api.extension.RegisterExtension;
+
+import io.quarkus.test.QuarkusUnitTest;
+import io.quarkus.vertx.web.RouteFilter;
+import io.vertx.ext.web.RoutingContext;
+
+public class VertxHeadersTest {
+
+    @RegisterExtension
+    static QuarkusUnitTest TEST = new QuarkusUnitTest()
+            .withApplicationRoot((jar) -> jar.addClasses(VertxFilter.class, JaxRsFilter.class, TestResource.class));
+
+    @Test
+    void testVaryHeaderValues() {
+        var headers = when().get("/test")
+                .then()
+                .statusCode(200)
+                .extract().headers();
+        assertThat(headers.getValues(HttpHeaders.VARY)).containsExactlyInAnyOrder("Origin", "Prefer");
+    }
+
+    public static class VertxFilter {
+        @RouteFilter
+        void addVary(final RoutingContext rc) {
+            rc.response().headers().add(HttpHeaders.VARY, "Origin");
+            rc.next();
+        }
+    }
+
+    @Provider
+    public static class JaxRsFilter implements ContainerResponseFilter {
+        @Override
+        public void filter(final ContainerRequestContext requestContext, final ContainerResponseContext responseContext)
+                throws IOException {
+            responseContext.getHeaders().add(HttpHeaders.VARY, "Prefer");
+        }
+    }
+
+    @Path("test")
+    public static class TestResource {
+
+        @GET
+        public String test() {
+            return "test";
+        }
+    }
+}
diff --git a/independent-projects/resteasy-reactive/server/runtime/src/main/java/org/jboss/resteasy/reactive/server/core/ServerSerialisers.java b/independent-projects/resteasy-reactive/server/runtime/src/main/java/org/jboss/resteasy/reactive/server/core/ServerSerialisers.java
index 4ad07b6084ea4..19da861778f6f 100644
--- a/independent-projects/resteasy-reactive/server/runtime/src/main/java/org/jboss/resteasy/reactive/server/core/ServerSerialisers.java
+++ b/independent-projects/resteasy-reactive/server/runtime/src/main/java/org/jboss/resteasy/reactive/server/core/ServerSerialisers.java
@@ -13,6 +13,7 @@
 import java.util.HashSet;
 import java.util.LinkedList;
 import java.util.List;
+import java.util.Locale;
 import java.util.Map;
 import java.util.Set;
 import java.util.concurrent.ConcurrentHashMap;
@@ -71,7 +72,13 @@ public void accept(ResteasyReactiveRequestContext context) {
         }
     };
 
-    private static final String CONTENT_TYPE = "Content-Type"; // use this instead of the Vert.x constant because the TCK expects upper case
+    private static final String CONTENT = "Content";
+    private static final String CONTENT_LOWER = "content";
+    private static final String TYPE = "Type";
+    private static final String TYPE_LOWER = "type";
+    private static final String LENGTH = "Length";
+    private static final String LENGTH_LOWER = "length";
+    private static final String CONTENT_TYPE = CONTENT + "-" + TYPE; // use this instead of the Vert.x constant because the TCK expects upper case
 
     static {
         primitivesToWrappers.put(boolean.class, Boolean.class);
@@ -484,13 +491,27 @@ public static void encodeResponseHeaders(ResteasyReactiveRequestContext requestC
         MultivaluedMap<String, Object> headers = response.getHeaders();
         for (Map.Entry<String, List<Object>> entry : headers.entrySet()) {
             if (entry.getValue().size() == 1) {
+                String header = entry.getKey();
+                boolean useSet = requireSingleHeader(header);
                 Object o = entry.getValue().get(0);
                 if (o == null) {
-                    vertxResponse.setResponseHeader(entry.getKey(), "");
+                    if (useSet) {
+                        vertxResponse.setResponseHeader(header, "");
+                    } else {
+                        vertxResponse.addResponseHeader(header, "");
+                    }
                 } else if (o instanceof CharSequence) {
-                    vertxResponse.setResponseHeader(entry.getKey(), (CharSequence) o);
+                    if (useSet) {
+                        vertxResponse.setResponseHeader(header, (CharSequence) o);
+                    } else {
+                        vertxResponse.addResponseHeader(header, (CharSequence) o);
+                    }
                 } else {
-                    vertxResponse.setResponseHeader(entry.getKey(), (CharSequence) HeaderUtil.headerToString(o));
+                    if (useSet) {
+                        vertxResponse.setResponseHeader(header, (CharSequence) HeaderUtil.headerToString(o));
+                    } else {
+                        vertxResponse.addResponseHeader(header, (CharSequence) HeaderUtil.headerToString(o));
+                    }
                 }
             } else {
                 List<CharSequence> strValues = new ArrayList<>(entry.getValue().size());
@@ -502,4 +523,15 @@ public static void encodeResponseHeaders(ResteasyReactiveRequestContext requestC
         }
     }
 
+    private static boolean requireSingleHeader(String header) {
+        if (!(header.startsWith(CONTENT) || header.startsWith(CONTENT_LOWER))) {
+            return false;
+        }
+        if (header.length() < CONTENT.length() + 2) {
+            return false;
+        }
+        String substring = header.substring(CONTENT.length() + 1).toLowerCase(Locale.ROOT);
+        return substring.equals(TYPE_LOWER) || substring.equals(LENGTH_LOWER);
+    }
+
 }