I first started lifting at a gym that used Nautilus equipment, where the staff promoted a Nautilus-style system of doing one set to failure. (That is, where you pick a weight that you can lift at least 8 times, but that you can’t lift more than 12 times.)
I understood right from the start that the system’s big attraction is for the gym owner: If everybody just did one set, the gym could sell two or three times as many memberships. However, I also found the physiology compelling: lifting as much as you can, and then attempting to lift a little more, is a powerful signal to your muscles that they need to become stronger.
I’ve generally stuck with single-set-to-failure workouts, because I’m lazy and find lifting boring: I want to get my workouts over with as quickly as possible and get on to something else.
Just lately, I’ve been experimenting with multiple sets. The reason is that, in the winter, my knees aren’t warmed up enough to lift a weight heavy enough to produce muscle failure in just 12 reps. If I try to push a weight that heavy, my knees hurt.
So, I’ve rearranged my lower-body workout. I’m now doing a first set of leg extension, leg curl, and leg press with a weight about one notch lower than my target weight, and then do a second set of all three with my target weight.
It’s working great. The first set serves as an excellent warm-up for my knees, getting the synovial fluid warmed up and flowing. The second set works the muscles to failure without knee pain. (On the leg press, I often do a third short set with an even higher weight, but that’s probably just because I’ve long been using too low of a weight, because it was all my knees could handle without a better warm-up.)
It’s working so well, I’m inclined to experiment with multiple sets for my upper body as well. I’m not sure it’s really a parallel situation, because I don’t have a joint issue that’s keeping me from reaching muscle failure, but doing the heavy workout with properly warmed-up joints just feels better, aside from not hurting.