diff --git a/Include/internal/pycore_pystate.h b/Include/internal/pycore_pystate.h
index da034e185a0..0073e205bea 100644
--- a/Include/internal/pycore_pystate.h
+++ b/Include/internal/pycore_pystate.h
@@ -317,12 +317,18 @@ _Py_IsMainInterpreter(PyThreadState* tstate)
 static inline int
 _Py_ThreadCanHandleSignals(PyThreadState *tstate)
 {
-    /* Use directly _PyRuntime rather than tstate->interp->runtime, since
-       this function is used in performance critical code path (ceval) */
     return (_Py_IsMainThread() && _Py_IsMainInterpreter(tstate));
 }
 
 
+/* Only execute pending calls on the main thread. */
+static inline int
+_Py_ThreadCanHandlePendingCalls(void)
+{
+    return _Py_IsMainThread();
+}
+
+
 /* Variable and macro for in-line access to current thread
    and interpreter state */
 
diff --git a/Misc/NEWS.d/next/Core and Builtins/2020-03-20-13-51-55.bpo-40010.QGf5s8.rst b/Misc/NEWS.d/next/Core and Builtins/2020-03-20-13-51-55.bpo-40010.QGf5s8.rst
new file mode 100644
index 00000000000..b0995134ed9
--- /dev/null
+++ b/Misc/NEWS.d/next/Core and Builtins/2020-03-20-13-51-55.bpo-40010.QGf5s8.rst	
@@ -0,0 +1,8 @@
+Optimize pending calls in multithreaded applications. If a thread different
+than the main thread schedules a pending call (:c:func:`Py_AddPendingCall`),
+the bytecode evaluation loop is no longer interrupted at each bytecode
+instruction to check for pending calls which cannot be executed. Only the
+main thread can execute pending calls.
+
+Previously, the bytecode evaluation loop was interrupted at each instruction
+until the main thread executes pending calls.
diff --git a/Python/ceval.c b/Python/ceval.c
index 86aa2253899..c80ee4b463c 100644
--- a/Python/ceval.c
+++ b/Python/ceval.c
@@ -149,7 +149,8 @@ COMPUTE_EVAL_BREAKER(PyThreadState *tstate,
         _Py_atomic_load_relaxed(&ceval->gil_drop_request)
         | (_Py_atomic_load_relaxed(&ceval->signals_pending)
            && _Py_ThreadCanHandleSignals(tstate))
-        | _Py_atomic_load_relaxed(&ceval2->pending.calls_to_do)
+        | (_Py_atomic_load_relaxed(&ceval2->pending.calls_to_do)
+           && _Py_ThreadCanHandlePendingCalls())
         | ceval2->pending.async_exc);
 }
 
@@ -180,9 +181,10 @@ static inline void
 SIGNAL_PENDING_CALLS(PyThreadState *tstate)
 {
     assert(is_tstate_valid(tstate));
+    struct _ceval_runtime_state *ceval = &tstate->interp->runtime->ceval;
     struct _ceval_state *ceval2 = &tstate->interp->ceval;
     _Py_atomic_store_relaxed(&ceval2->pending.calls_to_do, 1);
-    _Py_atomic_store_relaxed(&ceval2->eval_breaker, 1);
+    COMPUTE_EVAL_BREAKER(tstate, ceval, ceval2);
 }
 
 
@@ -606,8 +608,8 @@ handle_signals(PyThreadState *tstate)
 static int
 make_pending_calls(PyThreadState *tstate)
 {
-    /* only service pending calls on main thread */
-    if (!_Py_IsMainThread()) {
+    /* only execute pending calls on main thread */
+    if (!_Py_ThreadCanHandlePendingCalls()) {
         return 0;
     }