This works for me.
Excuse the code style please, I'm not used to VB.Net
Private Sub Button1_Click(ByVal sender As System.Object, ByVal e As System.EventArgs) Handles Button1.Click
MessageBox.Show("Save Called")
End Sub
Private Sub Button1_KeyDown(ByVal sender As System.Object, ByVal e As System.Windows.Forms.KeyEventArgs) Handles Button1.KeyDown
If e.Control Then
If e.KeyCode = Keys.S Then
Button1.PerformClick()
End If
End If
End Sub
I have just noticed that you want a lower case 's', so modify my code appropriately.