Purpose Stress-related factors influence the adaptation to life after acute myocardial infarction (AMI), including return to work. The goal of this study was to investigate the effect of work-related stress, (expressed by the effort-reward imbalance (ERI) model) on return to work after AMI. Methods A longitudinal study with AMI patients was conducted in order to assess associations between the independent variables effort, reward, ERI and overcommitment and the outcome return to work after AMI. Return to work was inquired at 6 months follow-up. Logistic regression models were applied in the analysis. The fully-adjusted model included demographic, clinical, social, stress-related and health-related quality of life (HRQOL) covariables. Results Of the 346 enrolled patients aged 31 to 82 years, 239 (69.1%) were included in the regression analysis. In the unadjusted model ERI presented an odds ratio (OR) of 1.72 (95% confidence interval (CI) 0.86–3.42). Associations for effort and overcommitment were 0.98 (95% CI 0.83–1.15) and 1.09 (95% CI 0.99–1.18). However, reward showed a significantly inverse association with return to work with an OR of 0.90 (95% CI 0.83–0.99). In the fully adjusted model the OR of ERI decreased to 1.20 (95% CI 0.49–2.96). Effort, reward and overcommitment also showed attenuated ORs without significant results in all models. Diabetes mellitus, current smoking, low physical and low mental HRQOL presented significantly negative relations with return to work. Conclusions Work-related stress appears less important than HRQOL and resilience in terms of return to work after AMI.