This is going to depend largely on who is answering, but personally, yes I think there is a significant difference.
Typically, the 45ACP recoil will move the handgun more than a 40S&W, but the velocity at which the recoil distance is traveled is slower than the 40S&W. This is probably due to the much lower PSI rating of the 45ACP, even in +p loads. So while followup shots on the 45ACP take longer, repeated recoil is, in my opinion, much more forgiving to the hands.
I've got no problem firing 40S&W in small doses, but if I exceed 200 rounds a session, I do begin to notice fatigue and sometimes physical wear (blisters). I've never gotten tired of shooting 45ACP, or 9mm for that matter
Think of the 40S&W as a midrange musical instrument (trumpet) and the 45ACP as a lower band, bass musical instrument (saxophone or maybe even tuba).
[Edit]: I've seen plenty of people who claim they notice little-to-no difference between 40S&W and 45ACP recoils. To be honest, I envy these guys.


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