The purpose of this study was to compare the effect of low- versus high-load resistance training (RT) on muscular adaptations in well-trained subjects. Eighteen young men experienced in RT were matched according to baseline strength and then randomly assigned to 1 of 2 experimental groups: a low-load RT routine (LL) where 25-35 repetitions were performed per set per exercise (n = 9) or a high-load RT routine (HL) where 8-12 repetitions were performed per set per exercise (n = 9). During each session, subjects in both groups performed 3 sets of 7 different exercises representing all major muscles. Training was performed 3 times per week on nonconsecutive days, for a total of 8 weeks. Both HL and LL conditions produced significant increases in thickness of the elbow flexors (5.3 vs. 8.6%, respectively), elbow extensors (6.0 vs. 5.2%, respectively), and quadriceps femoris (9.3 vs. 9.5%, respectively), with no significant differences noted between groups. Improvements in back squat strength were significantly greater for HL compared with LL (19.6 vs. 8.8%, respectively), and there was a trend for greater increases in 1 repetition maximum (1RM) bench press (6.5 vs. 2.0%, respectively). Upper body muscle endurance (assessed by the bench press at 50% 1RM to failure) improved to a greater extent in LL compared with HL (16.6 vs. -1.2%, respectively). These findings indicate that both HL and LL training to failure can elicit significant increases in muscle hypertrophy among well-trained young men; however, HL training is superior for maximizing strength adaptations.