This study aimed to assess the effects of physically demanding work - measured as energy expenditure (EE) during occupational physical activities (OPA) - on risk of acute myocardial infarction (AMI) among men with and without preexisting ischemic heart disease (IHD). The 20-year prospective study examined 1891 middle-aged working men using absolute (kcal/day) and relative (relative aerobic strain and percent oxygen uptake reserve) measures of EE. Linear and quadratic hazard models were explored in Cox regression analyses adjusting for 19 potential confounders and considering interactions with baseline IHD. Relative EE measures were positively associated with 20-year incidence of AMI in linear and quadratic hazard models and interacted with IHD. Each 10% increase of relative aerobic strain increased AMI risk by 18% among men without IHD [hazard ratio (HR) 1.18, 95% confidence interval (95% CI) 1.08-1.28, P=0.001] and by 8% among men with IHD (HR 1.08, 95% CI 0.98-1.20, P=0.129) in fully adjusted linear models. Results for quadratic models and percent oxygen uptake reserve were similar. Absolute EE did not predict AMI. Age, baseline IHD, systolic blood pressure, anti-hypertensive medication, body mass index, blood glucose, low-density lipoprotein cholesterol, cholesterol-lowering medication, mental stress, and smoking were independently associated with AMI, but not income, social support, alcohol, or conditioning leisure-time physical activity. In contrast to absolute EE, relative workload measures that take individual fitness into account were positively associated with AMI incidence among men without IHD. For men with IHD, associations were also positive but weaker possibly due to healthy worker selection effects. These findings provide evidence for a positive association between OPA and AMI among men.