Background <p>Psychosocial stress is increasingly recognized as an independent risk factor for cardiovascular disease. However, the long-term impact of cumulative stressful life events on the risk of myocardial infarction (MI) and mortality in the general population remains underexplored. This study investigates the association between lifetime exposure to stressful life events and the risk of non-fatal MI, MI-related mortality, and all-cause mortality.</p> Methods <p>We analyzed data from 21,830 participants aged ≥ 40 in the Tromsø Study (1994–2020). Exposure to stressful life events was assessed retrospectively in 2015–2016 and categorized into groups based on the total number of reported events. Cox proportional hazards models were used to estimate hazard ratios for non-fatal MI, MI-related mortality, and all-cause mortality, adjusting for age, sex, lifestyle, treatment, and biological factors.</p> Results <p>Participants reporting four or more stressful life events experienced non-fatal MI on average 3.7 years earlier, MI-related mortality 12.3 years earlier, and all-cause mortality 9.5 years earlier than those without exposure to stressful life events. Higher exposure to stressful life events was associated with increased risk of non-fatal MI (hazard ratio 1.06 per additional event; 95% confidence interval: 1.01–1.10), MI-related mortality (hazard ratio 1.25; 95% confidence interval: 1.07–1.46), and all-cause mortality (hazard ratio 1.14; 95% confidence interval: 1.08–1.20). These associations persisted after adjustment for traditional cardiovascular risk factors.</p> Conclusions <p>Lifetime exposure to stressful life events is associated with risks of MI, MI-related mortality, and all-cause mortality. Our findings highlight the importance of considering psychosocial stress in cardiovascular risk assessments and support the integration of screening for stressful life events into preventive cardiology.</p>