Objective To investigate the single and combined effectiveness of commonly prescribed secondary preventive medications (post-acute myocardial infarction (AMI)) in reducing overall all-cause mortality and by gender. Design Population-based longitudinal cohort study. Setting Western Australia, Australia. Participants 9580 individuals aged 65 years to 84 years who were admitted to hospital with their first AMI diagnosis between 1 January 1995 and 1 January 2006. Main outcome measures Time to death from any cause out to 11 years after first AMI, identified from registry data, was the primary outcome measure. Cardiovascular drugs dispensed within 28 days following hospital discharge were identified as main exposure categories. Results In total, 975 deaths occurred during 1 year follow-up, culminating to 3247 by 11 years. 1-year risk of death was significantly reduced for all drug combinations, but not for drugs dispensed in isolation. Out to 11 years, only combinations of 'β-blockers and statins' (with or without ACE inhibitors/angiotensin II receptor blockers (ACEi/ARB)) provided significant reductions in risk of all-cause mortality. In men, the greatest reduction in risk was associated with being dispensed 'β-blockers and statins' (HR 0.46, 95% CI 0.36 to 0.58), whereas women benefited most from being dispensed 'β-blockers, statins and ACEi/ARBs' (HR 0.77, 95% CI 0.60 to 0.99). Conclusions The combination of 'β-blockers and statins' (with or without ACEi/ARB) dispensed within 28 days postdischarge was associated with the greatest long-term survival following an AMI. Our observations of significantly reduced mortality risk in men (compared with women) who were dispensed 'β-blockers and statins', or 'β-blockers and ACEi/ARBs', warrants further investigation.