OBJECTIVE: To document the trends in reperfusion therapy for ST segment elevation myocardial infarction (STEMI) in Switzerland. DESIGN: National prospective multicentre registry, AMIS Plus (acute myocardial infarction and unstable angina in Switzerland), of patients admitted with acute coronary syndromes. SETTING: 54 hospitals of varying size and capability in Switzerland. PATIENTS: 7098 of 11 845 AMIS Plus patients who presented with ST segment elevation or left bundle branch block on the ECG at admission. MAIN OUTCOME MEASURES: In-hospital mortality and its predictors at admission by multivariate analysis. RESULTS: The proportion of patients treated by primary percutaneous coronary intervention (PCI) progressively increased from 1997 to 2002, while the proportion with thrombolysis or no reperfusion decreased (from 8.0% to 43.1%, from 47.2% to 25.6%, and from 44.8% to 31.4%, respectively). Overall in-hospital mortality decreased over the study period from 12.2% to 6.7% (p < 0.001). Main in-hospital mortality predictors by multivariate analysis were primary PCI (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.33 to 0.81), thrombolysis (OR 0.63, 95% CI 0.47 to 0.83), and Killip class III (OR 3.61, 95% CI 2.49 to 5.24) and class IV (OR 5.97, 95% CI 3.51 to 10.17) at admission. When adjusted for the year, multivariate analysis did not show PCI to be significantly superior to thrombolysis for in-hospital mortality (OR 1.2 for PCI better, 95% CI 0.8 to 1.9, p = 0.42). CONCLUSION: Primary PCI has become the preferred mode of reperfusion for STEMI since 2002 in Switzerland, whereas use of intravenous thrombolysis has decreased from 1997 to 2002. Furthermore, there was a major reduction of in-hospital mortality over the same period.