For years, bodybuilders were told to first perform exercises which utilize multiple muscle fibers, such as the squat, followed by exercises for isolation, such as the leg extension. This is commonly referred to as the “size principle of motor unit recruitment.” 

Maximal muscle growth requires you to recruit as many muscle fibers as possible during exercise, which is the reason many bodybuilders perform squats first—because the exercise utilizes many different muscle fibers. For gaining muscle size, your training goal should be to recruit as many motor units as possible during exercise to get the fastest results for muscle growth. 

This has been the bodybuilding way of life for decades, but recently a study in the Journal of Medicina Sportiva found this may not be true. The research paper was a critical review on exercise sequence and muscle growth and has challenged the size principle theory. The authors reported that two new studies showed no significant difference between groups in strength gains for any of the exercises or any significant difference in muscular hypertrophy when small muscle groups were performed first compared to large muscle groups. 

The key finding was that when repetitions were standardized for workouts comparing small vs. large muscle groups performed first, the results were the same. The research paper went on to report that many studies that have examined small vs. large muscle groups being performed first failed to control for repetitions completed. The reviewer noted that some of these studies reported that significantly fewer repetitions were performed in subsequent sets of an exercise when they were performed later in a resistance-training session, compared with when they were performed earlier in the session. The lead author concluded, “There is very little evidence to suggest that any specific sequence of exercise affects strength gains or muscular hypertrophy.” 

As long as volume remains equal for workouts, it should make very little difference which exercise is performed first. – FLEX