Background: Amid increasing concerns about rising obesity rates and unhealthy lifestyle behaviours, physical activity (PA) is seen as a prophylactic to many chronic conditions affecting men. Men respond best to community-based PA programmes, using gender-specific promotional and delivery strategies. 'Men on the Move' (MOM) was developed on this basis and targeted inactive adult men in Ireland. Methods: Sedentary men (n = 927; age = 50.7 ± 10.9 years; weight = 92.7 ± 16.0 kg; METS = 6.06 ± 2.13) were recruited across eight counties: four 'intervention group' (IG; n = 501) and four 'comparison-in-waiting group' (CG; n = 426). The MOM programme involved structured group exercise twice weekly for 12 weeks (W), along with health-related workshops with the groups maintained up to 52 W. Primary outcome measures [aerobic fitness, bodyweight and waist circumference (WC)] together with self-administered questionnaires were used to gather participant data at baseline, 12, 26 and 52 W. Results: Results show a net positive effect on aerobic fitness, bodyweight and WC, with significant (P < 0.05) net change scores observed in the IG compared to the CG (METS: 12 W = +2.20, 26 W = +1.89, 52 W = +0.92; weight: 12 W =-1.72 kg, 26 W =-1.95 kg, 52 W =-1.89 kg; WC: 12 W =-4.54 cm, 26 W =-2.69 cm, 52 W =-3.16 cm). The corresponding reduction in cardiovascular disease risk is particularly significant in the context of a previously inactive and overweight cohort. The high 'dropout' (42.7% presenting at 52 W), however, is of particular concern, with 'dropouts' having lower levels of aerobic fitness and higher bodyweight/WC at baseline. Conclusions: Notwithstanding dropout issues, findings address an important gap in public health practice by informing the translational scale-up of a small controllable gender-specific PA intervention, MOM, to a national population-based PA intervention targeting inactive men.