The aim of the present study was to investigate whether the implementation of an early invasive strategy for unselected patients with acute myocardial infarction (AMI) would be associated with reduced long-term mortality compared to a conservative approach. In this prospective observational cohort study of consecutive patients admitted for AMI in 2003 (conservative cohort, n = 311) and 2006 (invasive cohort [IC], n = 307), an 11% absolute and 41% relative reduction in 1-year mortality was found for patients with AMI in the IC compared to the conservative cohort (p = 0.001). These findings were consistent after adjustment for age, gender, previous AMI, previous stroke, diabetes, smoking status, previous left ventricular systolic dysfunction, and serum creatinine at admission (hazard ratio 0.54, 95% confidence interval 0.38 to 0.78) and Global Registry of Acute Coronary Events risk score (hazard ratio 0.67, 95% confidence interval 0.46 to 0.97). More patients with ST-segment elevation myocardial infarction received primary percutaneous coronary intervention in the IC (57% vs 3%, p <0.001), and a sixfold (25% vs 4%, p <0.001) increase in early percutaneous coronary intervention (<72 hours) for patients with non–ST-segment elevation myocardial infarction was observed. A greater proportion of patients in the IC received clopidogrel, aspirin, and statins during follow-up; otherwise, the secondary prevention measures were similar in the 2 cohorts. In conclusion, the introduction of a strategy for routine transfer to a high-volume percutaneous coronary intervention center for early invasive therapy was accompanied by a substantial reduction in mortality among unselected patients with AMI. Differences in unmeasured confounders might have accounted for a part of the difference in outcome.