OBJECTIVES: We sought to evaluate the association between physical activity levels and the clinical outcome at presentation, as well as the 30-day prognosis of hospitalized patients with acute coronary syndromes (ACS). BACKGROUND: Regular physical activity has been associated with decreased risk of coronary heart disease. However, less is known about the effects of life-long physical activity on ACS prognosis. METHODS: From October 2003 to September 2004, a sample of 6 hospitals located in urban and rural Greek regions were selected, and almost all of their ACS patients were enrolled into the study (2,172 patients were included in the study; 76% men and 24% women). Logistic regression models were applied to evaluate the effect of physical activity status (as assessed using the International Physical Activity Questionnaire) on in-hospital mortality and the 30-day outcome of cardiovascular events (death or rehospitalization due to cardiovascular disease). RESULTS: An inverse association was observed between the level of physical activity and troponin I levels at presentation (p = 0.01). Moreover, after taking into account various potential confounders, physical activity was associated with a 0.56-fold (95% confidence interval [CI] 0.32 to 0.90) lower odds of in-hospital mortality and a 0.80-fold (95% CI 0.50 to 0.99) lower odds of cardiovascular events within the first month after discharge. CONCLUSION: In conclusion, physical activity is associated with a reduced severity of ACS, reduced in-hospital mortality rates, and improved short-term prognosis.