Objective: Compare dietary supplement use and associated factors between younger and older men exercising at gyms (Cape Town). Design: Cross-sectional comparative study (self-administered questionnaire). Setting: Younger (21–31 years) and older (≥ 45) men exercising at gyms (Cape Town). Subjects: 210 younger and 91 older men. Outcome measures: Supplement use (frequency, reason, effectiveness, information sources, label use) and gym exercise profile and goals. Results: 80.6% younger and 81.3% older men had used supplements in the past 6 months. Younger men were more likely to use energy drinks (50% vs. 29.7%; p = 0.014), protein bars (18.1% vs. 7.7%; p = 0.038), protein powders (50% vs. 8.8%; p < 0.001), amino acids (15.2% vs. 2.2%; p = 0.004), weight gainers (10.9 vs. 1.1%; p = 0.011), recovery drinks (13.8 vs. 6.6%; p = 0.026), creatine (34.3 vs. 4.4%; p < 0.001), glutamine (22.4 vs. 7.7%; p = 0.004), arginine (8.6 vs. 0%; p = 0.016), pre-train (11.9 vs. 3.3%; p = 0.04) and fat burner (11.4 vs. 0%; p = 0.004). Multi-vitamins, vitamin C and B vitamins were consumed by both groups. Younger men spent more hours/week exercising in a gym (6.1 ± 4.0 vs. 4.0 ± 1.7; p < 0.001) and doing strength exercises (4.0 ± 2.9 vs. 1.6 ± 1.2; p < 0.001). The main exercising goal was building muscle/strength (38.8%), to stay fit (21.8%) or to look good (15.5%) for younger men and to stay fit (41.6%) or healthy (41.6%) for older men (p < 0.001). Conclusions: Younger and older men exercising in select gyms in Cape Town use a variety of supplements. Supplement use and exercising by younger men seem to focus on muscle building/strength and fitness; that of older men on improvement of fitness and health.