The aim of this study was to investigate the impact of protocols equalized by the time under tension (TUT) but composed of different repetition durations and repetitions numbers on muscle activation and blood lactate concentration. Twenty-two males with previous experience in resistance training performed 2 training protocols (A and B) with the Smith machine bench press exercise, both with 3 sets, 3 minutes' rest, and 60% of 1 repetition maximum (1RM). Protocol A consisted of 6 repetitions with a 6-second repetition duration for each repetition, whereas in Protocol B the subjects performed 12 repetitions with a 3-second repetition duration for each repetition. Muscular activation was measured in the anterior deltoid, pectoralis major, and triceps brachii muscles while performing the 2 protocols, and the normalized root mean square of the electromyographic signal (EMGRMS) was calculated for each set. Blood lactate concentrations were measured during and until 12 minutes after the completion of each protocol. The results showed that the EMGRMS of all muscles increased during the sets and was higher in Protocol B when compared with Protocol A. Likewise, blood lactate concentrations also increased throughout the sets and were higher in Protocol B both during and after the completion of each training session. The data obtained in this study show that training protocols conducted with the same TUT, but with different configurations, produce distinct neuromuscular and metabolic responses so that performing higher repetition numbers with shorter repetition durations might be a more appropriate strategy to increase muscle activation and blood lactate concentration.