BACKGROUND: Regionalization of care for ST-segment elevation myocardial infarction (STEMI) has been advocated, although its effect on processes of care and clinical outcomes remains uncertain. AIM: To assess the impact of a regional system of care on provision of reperfusion therapy for STEMI patients relative to control hospitals. METHODS: We analysed the original data from two nationwide prospective cohort studies conducted in 2000 and 2005, respectively. Overall, 160 hospitals participated in both studies, including seven hospitals involved in a regional system of care implemented in the Northern Alps in 2002 and 153 control hospitals located in other French areas. RESULTS: A total of 102 and 2377 STEMI patients were enrolled in Northern Alps and control hospitals, respectively. Overall, patients enrolled in 2005 were more likely to receive any reperfusion therapy (60% vs 52%; P < 0.001), prehospital fibrinolysis (33% vs 15%; P < 0.001), and primary percutaneous coronary intervention (32% vs 26%; P < 0.001) than those enrolled in 2000. However, the regional system of care was associated with a larger absolute change in the use of prehospital fibrinolysis (45.0 vs 17.0; P = 0.02) and rescue or early routine coronary angiography or intervention after fibrinolysis (35.3 vs 15.2; P = 0.01). Patients enrolled in 2005 had lower adjusted hazard ratios for death (0.70, 95% confidence interval 0.57-0.87; P = 0.001), with no significant interaction between study groups. CONCLUSION: Regionalization of care for STEMI patients improves access to reperfusion therapy, although its impact on clinical outcomes deserves further study.