Background: Cardiovascular diseases, with myocardial infarction (MI) on the leading position, remain a serious health care issue and socio-economic burden. Nevertheless, factors influencing the return of patients to the professional activity are not fully understood. Cardiac rehabilitation may have a positive impact on the return to professional activity after MI. However, no study among participants in the comprehensive care after myocardial infarction (CCMI) model (in Polish: “KOS-zawał”) evaluated this issue so far. The aim of the study was to evaluate factors influencing the return to work and duration of the sick leave after MI among patients who participated in the CCMI in a single reference cardiology centre in Poland. Material and Methods: In total, 144 patients were screened retrospectively. Out of them, 105 were included in the analysis. All patients were treated with direct percutaneous coronary intervention according to current European Society of Cardiology guidelines and participated in cardiac rehabilitation within the CCMI program, therefore had been provided optimal and modern therapeutic approach. Data was collected based on patients’ medical records and information furnished by the insurer. Results: Out of 105 patients analysed, 93 (88,6%) returned to work. A positive predictor of returning to work was male sex. Predictors of a prolonged return to work were older age and female sex. Completing rehabilitation, anthropometric factors, biochemical factors or results of post-MI echocardiographic examination did not influence the return to professional activity. Conclusions: A relatively large percentage of patients after MI and in the CCMI program returns to professional activity. Main factors of prolonged sick leave are older age and female sex. Med Pr Work Health Saf. 2024;75(6):501–510