The purpose of this investigation was to compare the effects of single-set strength training and 3-set strength training during the early phase of adaptation in 18 untrained male subjects (age, 20–30 years). After initial testing, subjects were randomly assigned to either the 3L-1U group (n = 8), which trained 3 sets in leg exercises and 1 set in upper-body exercises, or the 1L-3U group (n = 10), which trained 1 set in leg exercises and 3 sets in upper-body exercises. Testing was conducted at the beginning and at the end of the study and consisted of 2 maximal isometric tests (knee extension and bench press) and 6 maximal dynamic tests (1 repetition maximum [1RM] tests). Subjects trained 3 days per week for 6 weeks. After warm-up, subjects performed 3 leg exercises and 4 upper-body exercises. In both groups, each set consisted of 7 repetitions (reps) with the load supposed to induce muscular failure after the seventh rep (7RM load). After 6 weeks of training, 1RM performance in all training exercises was significantly increased (10–26%, p < 0.01) in both groups. The relative increase in 1RM load in the 3 leg exercises was significantly greater in the 3L-1U group than in the 1L-3U group (21% vs. 14%, p = 0.01). However, the relative increase in 1RM load in the 3 upper-body exercises was similar in the 3L-1U group (16%) and the 1L-3U group (14%). These results show a superior adaptation to 3-set strength training, compared with 1-set strength training, in leg exercises but not in upper-body exercises during the early phase of adaptation.