I think if you do some searching, you will find a LOT on this topic. My own opinion is that if I wanted a caliber larger than 9mm, then I would go directly to 45ACP. Some disagree, but this is just my feelings. Especially in smaller pistols, I feel there is more of a flip to the .40 whereas the .45 is more of a rearward push. I don't currently feel the need for a larger caliber, but if I do in the future, I will be going straight to 45ACP. Also, atleast in my experiences, 45ACP ammo is a little easier to find than 40S&W. The price difference in minimal as well (atleast in my area).