diff --git a/pex/environment.py b/pex/environment.py
index c1afbb4aa..d40ea1765 100644
--- a/pex/environment.py
+++ b/pex/environment.py
@@ -130,6 +130,7 @@ def __init__(self, pex, pex_info, interpreter=None, **kw):
       platform=platform_name,
       **kw
     )
+    self._target_interpreter_env = self._interpreter.identity.pkg_resources_env(platform_name)
     self._supported_tags.extend(platform.supported_tags(self._interpreter))
     TRACER.log(
       'E: tags for %r x %r -> %s' % (self.platform, self._interpreter, self._supported_tags),
@@ -161,7 +162,7 @@ def _resolve(self, working_set, reqs):
     # Resolve them one at a time so that we can figure out which ones we need to elide should
     # there be an interpreter incompatibility.
     for req in reqs:
-      if req.marker and not req.marker.evaluate():
+      if req.marker and not req.marker.evaluate(environment=self._target_interpreter_env):
         TRACER.log('Skipping activation of `%s` due to environment marker de-selection' % req)
         continue
       with TRACER.timed('Resolving %s' % req, V=2):
diff --git a/pex/resolver.py b/pex/resolver.py
index c74c09a0d..4f19d5f4a 100644
--- a/pex/resolver.py
+++ b/pex/resolver.py
@@ -220,6 +220,8 @@ def __init__(self, allow_prereleases=None, interpreter=None, platform=None, use_
     self._interpreter = interpreter or PythonInterpreter.get()
     self._platform = self._maybe_expand_platform(self._interpreter, platform)
     self._allow_prereleases = allow_prereleases
+    platform_name = self._platform.platform
+    self._target_interpreter_env = self._interpreter.identity.pkg_resources_env(platform_name)
     self._supported_tags = self._platform.supported_tags(
       self._interpreter,
       use_manylinux
@@ -259,8 +261,17 @@ def build(self, package, options):
         'Could not get distribution for %s on platform %s.' % (package, self._platform))
     return dist
 
+  def is_resolvable_in_target_interpreter_env(self, resolvable):
+    if not isinstance(resolvable, ResolvableRequirement):
+      return True
+    elif resolvable.requirement.marker is None:
+      return True
+    else:
+      return resolvable.requirement.marker.evaluate(environment=self._target_interpreter_env)
+
   def resolve(self, resolvables, resolvable_set=None):
-    resolvables = [(resolvable, None) for resolvable in resolvables]
+    resolvables = [(resolvable, None) for resolvable in resolvables
+                   if self.is_resolvable_in_target_interpreter_env(resolvable)]
     resolvable_set = resolvable_set or _ResolvableSet()
     processed_resolvables = set()
     processed_packages = {}
@@ -297,9 +308,7 @@ def resolve(self, resolvables, resolvable_set=None):
         new_parent = '%s->%s' % (parent, resolvable) if parent else str(resolvable)
         # We patch packaging.markers.default_environment here so we find optional reqs for the
         # platform we're building the PEX for, rather than the one we're on.
-        with patched_packing_env(
-          self._interpreter.identity.pkg_resources_env(self._platform.platform)
-        ):
+        with patched_packing_env(self._target_interpreter_env):
           resolvables.extend(
             (ResolvableRequirement(req, resolvable.options), new_parent) for req in
             distribution.requires(extras=resolvable_set.extras(resolvable.name))
diff --git a/tests/test_integration.py b/tests/test_integration.py
index 78116aee4..36bee7ac5 100644
--- a/tests/test_integration.py
+++ b/tests/test_integration.py
@@ -1112,7 +1112,7 @@ def test_setup_interpreter_constraint():
 @pytest.mark.skipif(IS_PYPY,
                     reason='Our pyenv interpreter setup fails under pypy: '
                            'https://github.com/pantsbuild/pex/issues/477')
-def test_setup_python_multiple():
+def test_setup_python_multiple_transitive_markers():
   py27_interpreter = ensure_python_interpreter(PY27)
   py36_interpreter = ensure_python_interpreter(PY36)
   with temporary_dir() as out:
@@ -1143,3 +1143,50 @@ def test_setup_python_multiple():
 
       stdout = subprocess.check_output(both_program)
       assert to_bytes(os.path.realpath(py36_interpreter)) == stdout.strip()
+
+
+@pytest.mark.skipif(IS_PYPY,
+                    reason='Our pyenv interpreter setup fails under pypy: '
+                           'https://github.com/pantsbuild/pex/issues/477')
+def test_setup_python_direct_markers():
+  py36_interpreter = ensure_python_interpreter(PY36)
+  with temporary_dir() as out:
+    pex = os.path.join(out, 'pex.pex')
+    results = run_pex_command(['subprocess32==3.2.7; python_version<"3"',
+                               '--disable-cache',
+                               '--python-shebang=#!/usr/bin/env python',
+                               '--python={}'.format(py36_interpreter),
+                               '-o', pex])
+    results.assert_success()
+
+    py2_only_program = [pex, '-c', 'import subprocess32']
+
+    with environment_as(PATH=os.path.dirname(py36_interpreter)):
+      with pytest.raises(subprocess.CalledProcessError):
+        subprocess.check_call(py2_only_program)
+
+
+@pytest.mark.skipif(IS_PYPY,
+                    reason='Our pyenv interpreter setup fails under pypy: '
+                           'https://github.com/pantsbuild/pex/issues/477')
+def test_setup_python_multiple_direct_markers():
+  py36_interpreter = ensure_python_interpreter(PY36)
+  py27_interpreter = ensure_python_interpreter(PY27)
+  with temporary_dir() as out:
+    pex = os.path.join(out, 'pex.pex')
+    results = run_pex_command(['subprocess32==3.2.7; python_version<"3"',
+                               '--disable-cache',
+                               '--python-shebang=#!/usr/bin/env python',
+                               '--python={}'.format(py36_interpreter),
+                               '--python={}'.format(py27_interpreter),
+                               '-o', pex])
+    results.assert_success()
+
+    py2_only_program = [pex, '-c', 'import subprocess32']
+
+    with environment_as(PATH=os.path.dirname(py36_interpreter)):
+      with pytest.raises(subprocess.CalledProcessError):
+        subprocess.check_call(py2_only_program)
+
+    with environment_as(PATH=os.path.dirname(py27_interpreter)):
+      subprocess.check_call(py2_only_program)