What is the best number of sets to use to gain the most muscle?

The most efficient way to build muscle is to periodize your training. That means you don't focus on a specific set/rep scheme but instead go through a variety. For one period of time, you might be doing lower repetitions and high rest between sets. For another period, you may be doing higher repetitions and less rest, etc. While it is easy to create "systems" and sell them in magazines saying, for example, that 10 - 12 reps is optimal for muscle growth, the truth is that there are a lot more factors that come into play.