This study conducted a secondary survey based on the hypothesis that the “total mechanical activation of fast-twitch fibers in the muscles determines the effects of muscle hypertrophy”, with resistance training of the knee extensor muscles as the target because of its importance in preventing sarcopenia. Using a mathematical model that estimates the mechanical activation of each muscle fiber (fast-twitch and slow-twitch fiber) during exercise, which was developed in a previous study, we estimated the total mechanical activation of fast-twitch fibers in 30 training programs described in 23 selected previous studies on leg extension exercise programs and their muscle hypertrophy effect. With the estimated value and other factors of the training effect described in previous studies (training volume, etc.) as explanatory variables and muscle hypertrophy effect as an objective variable, we performed multiple regression analysis. The results revealed that the training effect was related to total mechanical activation of the fast-twitch fibers (standardized partial regression coefficient: 0.66), training load (standardized partial regression coefficient, 0.29) and number of sets (standardized partial regression coefficient: −0.37). The total mechanical activation of fast-twitch fibers was the strongest determinant of the muscle hypertrophy effect. In addition, we predicted the relationship between the level of the training effect of leg extension exercise and program variables. This study is the first to demonstrate “the relationship between total mechanical activation of fast-twitch fibers and muscle hypertrophy effect” in the field of muscle physiology, and the first to elucidate the association between the program variables and the training effect.