This study investigated whether differences in neuromuscular performance and muscle hypertrophy occur between young and older men. Twenty-three young (29 ± 9 years) and 26 older men (64 ± 8 years) completed 10 weeks of high-volume, medium load "hypertrophic" resistance training with low frequency (twice per week) with 10 young (34 ± 11 years) and 11 older men (65 ± 3 years) acting as nontraining control subjects. Training consisted of 2-5 sets of 8-14 repetitions (1- to 2-minute rest). Lower-limb dynamic (leg press) and isometric maximum leg extension force, as well as lower-limb lean mass and vastus lateralis cross-sectional area were assessed before and after the training period. Training led to significant increases in 1 repetition maximum (1RM) leg press performance in both training groups (young: 13 ± 7%, p < 0.001; older: 14 ± 9%, p < 0.001). Performance improvements were accompanied by increased muscle activation, assessed by voluntary activation level (29 ± 51%, p ≤ 0.05) and electromyography amplitude (35 ± 51%, p < 0.01) in older men only. Conversely, only young men showed significantly increased lower-limb lean mass (2.4 ± 2.5%, p < 0.01). Furthermore, increases in 1RM performance and lower-limb lean mass were significantly related in young men only (r = 0.524, p = 0.01, n = 23). In conclusion, although high-volume, medium load "hypertrophic" resistance training may induce similar improvements in strength between young and older men, it appears that different mechanisms underpin these improvements.