diff --git a/base/inference.jl b/base/inference.jl
index 42b4d86cc2012..fdba556e21692 100644
--- a/base/inference.jl
+++ b/base/inference.jl
@@ -4471,10 +4471,18 @@ function inlining_pass(e::Expr, sv::InferenceState, stmts, ins)
                 elseif isa(aarg, Tuple)
                     newargs[i-2] = Any[ QuoteNode(x) for x in aarg ]
                 elseif isa(t, DataType) && t.name === Tuple.name && !isvatuple(t) &&
-                        effect_free(aarg, sv.src, sv.mod, true) && length(t.parameters) <= sv.params.MAX_TUPLE_SPLAT
-                    # apply(f,t::(x,y)) => f(t[1],t[2])
+                         length(t.parameters) <= sv.params.MAX_TUPLE_SPLAT
+                    if effect_free(aarg, sv.src, sv.mod, true)
+                        # apply(f,t::(x,y)) => f(t[1],t[2])
+                        tmpv = aarg
+                    else
+                        # apply(f,t::(x,y)) => tmp=t; f(tmp[1],tmp[2])
+                        tmpv = newvar!(sv, t)
+                        insert!(stmts, ins, Expr(:(=), tmpv, aarg))
+                        ins += 1
+                    end
                     tp = t.parameters
-                    newargs[i-2] = Any[ mk_getfield(aarg,j,tp[j]) for j=1:length(tp) ]
+                    newargs[i-2] = Any[ mk_getfield(tmpv,j,tp[j]) for j=1:length(tp) ]
                 else
                     # not all args expandable
                     return e
diff --git a/test/inference.jl b/test/inference.jl
index 54621e6c892c8..dfc4bf8d4375e 100644
--- a/test/inference.jl
+++ b/test/inference.jl
@@ -685,6 +685,21 @@ end
 aa20704(x) = x(nothing)
 @test code_typed(aa20704, (typeof(a20704),))[1][1].pure
 
+#issue #21065, elision of _apply when splatted expression is not effect_free
+function f21065(x,y)
+    println("x=$x, y=$y")
+    return x, y
+end
+g21065(x,y) = +(f21065(x,y)...)
+function test_no_apply(expr::Expr)
+    return all(test_no_apply, expr.args)
+end
+function test_no_apply(ref::GlobalRef)
+    return ref.mod != Core || ref.name !== :_apply
+end
+test_no_apply(::Any) = true
+@test all(test_no_apply, code_typed(g21065, Tuple{Int,Int})[1].first.code)
+
 # issue #20033
 # check return_type_tfunc for calls where no method matches
 bcast_eltype_20033(f, A) = Core.Inference.return_type(f, Tuple{eltype(A)})
@@ -692,4 +707,4 @@ err20033(x::Float64...) = prod(x)
 @test bcast_eltype_20033(err20033, [1]) === Union{}
 @test Base.return_types(bcast_eltype_20033, (typeof(err20033), Vector{Int},)) == Any[Type{Union{}}]
 # return_type on builtins
-@test Core.Inference.return_type(tuple, Tuple{Int,Int8,Int}) === Tuple{Int,Int8,Int}
+@test Core.Inference.return_type(tuple, Tuple{Int,Int8,Int}) === Tuple{Int,Int8,Int}
\ No newline at end of file