diff --git a/Include/cpython/pyerrors.h b/Include/cpython/pyerrors.h
index 0b43d75..de6548d 100644
--- a/Include/cpython/pyerrors.h
+++ b/Include/cpython/pyerrors.h
@@ -133,6 +133,7 @@
 /* In signalmodule.c */
 
 int PySignal_SetWakeupFd(int fd);
+PyAPI_FUNC(int) _PyErr_CheckSignals(void);
 
 /* Support for adding program text to SyntaxErrors */
 
diff --git a/Misc/NEWS.d/next/Core and Builtins/2019-01-11-14-46-08.bpo-35724.Wv79MG.rst b/Misc/NEWS.d/next/Core and Builtins/2019-01-11-14-46-08.bpo-35724.Wv79MG.rst
new file mode 100644
index 0000000..d2d74e5
--- /dev/null
+++ b/Misc/NEWS.d/next/Core and Builtins/2019-01-11-14-46-08.bpo-35724.Wv79MG.rst
@@ -0,0 +1,2 @@
+Signal-handling is now guaranteed to happen relative to the main
+interpreter.
diff --git a/Modules/signalmodule.c b/Modules/signalmodule.c
index 9d49cbd..f29720b 100644
--- a/Modules/signalmodule.c
+++ b/Modules/signalmodule.c
@@ -99,6 +99,7 @@
 #include "pythread.h"
 static unsigned long main_thread;
 static pid_t main_pid;
+static PyInterpreterState *main_interp;
 
 static volatile struct {
     _Py_atomic_int tripped;
@@ -185,6 +186,13 @@
 }
 #endif
 
+static int
+is_main(void)
+{
+    return PyThread_get_thread_ident() == main_thread &&
+        _PyInterpreterState_Get() == main_interp;
+}
+
 static PyObject *
 signal_default_int_handler(PyObject *self, PyObject *args)
 {
@@ -464,7 +472,7 @@
             return NULL;
     }
 #endif
-    if (PyThread_get_thread_ident() != main_thread) {
+    if (!is_main()) {
         PyErr_SetString(PyExc_ValueError,
                         "signal only works in main thread");
         return NULL;
@@ -486,7 +494,7 @@
     else
         func = signal_handler;
     /* Check for pending signals before changing signal handler */
-    if (PyErr_CheckSignals()) {
+    if (_PyErr_CheckSignals()) {
         return NULL;
     }
     if (PyOS_setsig(signalnum, func) == SIG_ERR) {
@@ -681,7 +689,7 @@
         return NULL;
 #endif
 
-    if (PyThread_get_thread_ident() != main_thread) {
+    if (!is_main()) {
         PyErr_SetString(PyExc_ValueError,
                         "set_wakeup_fd only works in main thread");
         return NULL;
@@ -1314,6 +1322,7 @@
 
     main_thread = PyThread_get_thread_ident();
     main_pid = getpid();
+    main_interp = _PyInterpreterState_Get();
 
     /* Create the module and add the functions */
     m = PyModule_Create(&signalmodule);
@@ -1607,15 +1616,24 @@
 int
 PyErr_CheckSignals(void)
 {
+    if (!is_main()) {
+        return 0;
+    }
+
+    return _PyErr_CheckSignals();
+}
+
+
+/* Declared in cpython/pyerrors.h */
+int
+_PyErr_CheckSignals(void)
+{
     int i;
     PyObject *f;
 
     if (!_Py_atomic_load(&is_tripped))
         return 0;
 
-    if (PyThread_get_thread_ident() != main_thread)
-        return 0;
-
     /*
      * The is_tripped variable is meant to speed up the calls to
      * PyErr_CheckSignals (both directly or via pending calls) when no
@@ -1687,8 +1705,9 @@
 PyOS_InterruptOccurred(void)
 {
     if (_Py_atomic_load_relaxed(&Handlers[SIGINT].tripped)) {
-        if (PyThread_get_thread_ident() != main_thread)
+        if (!is_main()) {
             return 0;
+        }
         _Py_atomic_store_relaxed(&Handlers[SIGINT].tripped, 0);
         return 1;
     }
@@ -1716,12 +1735,13 @@
     _clear_pending_signals();
     main_thread = PyThread_get_thread_ident();
     main_pid = getpid();
+    main_interp = _PyInterpreterState_Get();
 }
 
 int
 _PyOS_IsMainThread(void)
 {
-    return PyThread_get_thread_ident() == main_thread;
+    return is_main();
 }
 
 #ifdef MS_WINDOWS
diff --git a/Python/ceval.c b/Python/ceval.c
index 03456f6..439f4f1 100644
--- a/Python/ceval.c
+++ b/Python/ceval.c
@@ -379,9 +379,16 @@
     {
         return 0;
     }
+    /*
+     * Ensure that the thread isn't currently running some other
+     * interpreter.
+     */
+    if (_PyInterpreterState_GET_UNSAFE() != _PyRuntime.interpreters.main) {
+        return 0;
+    }
 
     UNSIGNAL_PENDING_SIGNALS();
-    if (PyErr_CheckSignals() < 0) {
+    if (_PyErr_CheckSignals() < 0) {
         SIGNAL_PENDING_SIGNALS(); /* We're not done yet */
         return -1;
     }