ABSTRACT Aim We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular markers. Methods Trained men (n=15, age: 23±3 y; training experience: 7±3 y) performed unilateral lower body training for 6 weeks (3x weekly), where single legs were assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within subjects repeated measures ANOVAs were performed on all dependent variables except tracer data, which was compared using dependent samples t-tests. Results A significant (p<0.05) interaction existed for unilateral leg extension 1RM (HV