diff --git a/changelog/760.bugfix.rst b/changelog/760.bugfix.rst
new file mode 100644
index 00000000..7e108858
--- /dev/null
+++ b/changelog/760.bugfix.rst
@@ -0,0 +1,3 @@
+Identify plugins by object identity when registering, looking up, unregistering,
+and excluding hook implementations. Distinct plugins which compare equal no
+longer interfere with each other's registrations or hook calls.
diff --git a/src/pluggy/_caller.py b/src/pluggy/_caller.py
index 52b02316..255323e6 100644
--- a/src/pluggy/_caller.py
+++ b/src/pluggy/_caller.py
@@ -7,7 +7,6 @@
 from collections.abc import Callable
 from collections.abc import Mapping
 from collections.abc import Sequence
-from collections.abc import Set as AbstractSet
 from typing import Any
 from typing import Final
 from typing import final
@@ -115,7 +114,7 @@ def is_historic(self) -> bool:
 
     def _remove_plugin(self, plugin: _Plugin) -> None:
         """Remove all hook implementations registered by the given plugin."""
-        remaining = [impl for impl in self._hookimpls if impl.plugin != plugin]
+        remaining = [impl for impl in self._hookimpls if impl.plugin is not plugin]
         if len(remaining) == len(self._hookimpls):
             raise ValueError(f"plugin {plugin!r} not found")
         self._hookimpls[:] = remaining
@@ -296,7 +295,7 @@ class _SubsetHookCaller(HookCaller):
         "_remove_plugins",
     )
 
-    def __init__(self, orig: HookCaller, remove_plugins: AbstractSet[_Plugin]) -> None:
+    def __init__(self, orig: HookCaller, remove_plugins: Mapping[int, _Plugin]) -> None:
         self._orig = orig
         self._remove_plugins = remove_plugins
         self.name = orig.name  # type: ignore[misc]
@@ -307,7 +306,7 @@ def _hookimpls(self) -> list[HookImpl]:
         return [
             impl
             for impl in self._orig._hookimpls
-            if impl.plugin not in self._remove_plugins
+            if id(impl.plugin) not in self._remove_plugins
         ]
 
     @property
diff --git a/src/pluggy/_manager.py b/src/pluggy/_manager.py
index 4994c867..e07f6258 100644
--- a/src/pluggy/_manager.py
+++ b/src/pluggy/_manager.py
@@ -208,7 +208,7 @@ def register(self, plugin: _Plugin, name: str | None = None) -> str | None:
                 f"{plugin_name}={plugin}\n{self._name2plugin}"
             )
 
-        if plugin in self._name2plugin.values():
+        if self.is_registered(plugin):
             raise ValueError(
                 "Plugin already registered under a different name: "
                 f"{plugin_name}={plugin}\n{self._name2plugin}"
@@ -396,7 +396,9 @@ def get_plugins(self) -> set[Any]:
 
     def is_registered(self, plugin: _Plugin) -> bool:
         """Return whether the plugin is already registered."""
-        return any(plugin == val for val in self._name2plugin.values())
+        return plugin is not None and any(
+            plugin is val for val in self._name2plugin.values()
+        )
 
     def get_canonical_name(self, plugin: _Plugin) -> str:
         """Return a canonical name for a plugin object.
@@ -421,7 +423,7 @@ def get_name(self, plugin: _Plugin) -> str | None:
         """Return the name the plugin is registered under, or ``None`` if
         is isn't."""
         for name, val in self._name2plugin.items():
-            if plugin == val:
+            if val is not None and plugin is val:
                 return name
         return None
 
@@ -632,12 +634,16 @@ def subset_hook_caller(
         """Return a proxy :class:`~pluggy.HookCaller` for the named hook which
         calls all registered plugins except the ones from remove_plugins."""
         orig: HookCaller = getattr(self.hook, name)
-        plugins_to_remove = set(remove_plugins)
+        # Retain the objects so removed plugin ids cannot be reused by new plugins.
+        plugins_to_remove = {id(plugin): plugin for plugin in remove_plugins}
         # Optimization: discard plugins to remove which don't actually implement
         # the hook, to make checks faster.
-        plugins_to_remove.intersection_update(
-            hookimpl.plugin for hookimpl in orig._hookimpls
-        )
+        hook_plugin_ids = {id(hookimpl.plugin) for hookimpl in orig._hookimpls}
+        plugins_to_remove = {
+            key: plugin
+            for key, plugin in plugins_to_remove.items()
+            if key in hook_plugin_ids
+        }
         # Optimization: if none of the plugins to remove actually implement the
         # hook, avoid the subset hook caller overhead.
         if not plugins_to_remove:
diff --git a/testing/test_pluginmanager.py b/testing/test_pluginmanager.py
index 06d645d7..3481d05b 100644
--- a/testing/test_pluginmanager.py
+++ b/testing/test_pluginmanager.py
@@ -37,6 +37,68 @@ def test_register_rejects_none(pm: PluginManager) -> None:
     assert not pm.is_registered(None)
 
 
+def test_register_distinct_equal_plugins(pm: PluginManager) -> None:
+    class Spec:
+        @hookspec
+        def myhook(self):
+            pass
+
+    class Plugin:
+        def __init__(self, value: str) -> None:
+            self.value = value
+
+        def __eq__(self, other):
+            return isinstance(other, Plugin)
+
+        @hookimpl
+        def myhook(self):
+            return self.value
+
+    pm.add_hookspecs(Spec)
+    first, second, unknown = Plugin("one"), Plugin("two"), Plugin("unknown")
+    assert first == second
+    pm.register(first, "one")
+    assert not pm.is_registered(second)
+    assert pm.get_name(second) is None
+    assert pm.get_hookcallers(second) is None
+    pm.register(second, "two")
+    assert pm.get_name(first) == "one"
+    assert pm.get_name(second) == "two"
+    assert pm.hook.myhook() == ["two", "one"]
+    assert not pm.is_registered(unknown)
+    assert pm.subset_hook_caller("myhook", [unknown]) is pm.hook.myhook
+    assert pm.subset_hook_caller("myhook", [second])() == ["one"]
+    assert pm.subset_hook_caller("myhook", [first])() == ["two"]
+    assert pm.subset_hook_caller("myhook", [first, second])() == []
+    assert pm.unregister(second) is second
+    assert pm.is_registered(first)
+    assert not pm.is_registered(second)
+    assert pm.hook.myhook() == ["one"]
+    with pytest.raises(ValueError, match="already registered"):
+        pm.register(first, "other")
+
+
+def test_plugin_registry_does_not_call_equality(pm: PluginManager) -> None:
+    class Plugin:
+        def __eq__(self, other):
+            raise AssertionError("plugin equality must not be called")
+
+    first, second = Plugin(), Plugin()
+    with pytest.raises(AssertionError, match="plugin equality must not be called"):
+        assert first == second
+    pm.register(first, "one")
+    pm.register(second, "two")
+    assert pm.is_registered(first)
+    assert pm.get_name(first) == "one"
+    assert pm.unregister(second) is second
+
+
+def test_blocked_name_is_not_a_registered_plugin(pm: PluginManager) -> None:
+    pm.set_blocked("blocked")
+    assert not pm.is_registered(None)
+    assert pm.get_name(None) is None
+
+
 def test_pm(pm: PluginManager) -> None:
     """Basic registration with objects"""