ST segment resolution (STR) predicts epicardial and microvascular reperfusion after primary percutaneous coronary intervention (PPCI) or thrombolysis for ST-elevation myocardial infarction. Immediate restoration of epicardial coronary flow, with improved microvascular perfusion, is much more likely with PPCI. However, the predictive value of immediate STR compared to 90 minutes after PPCI remains unknown. In 622 consecutive patients with ST-elevation myocardial infarction (mean age 59 ± 13 years), 217 had complete STR immediately after PPCI (group A), 188 had complete STR only at 90 minutes (group B), and 217 had incomplete STR at either point (group C). The primary end point was mortality and adverse cardiovascular events ([MACE] death, nonfatal repeat myocardial infarction, and heart failure). Group A had a greater left ventricular ejection fraction (53%, 47%, and 46%, p <0.001) and lower all-cause mortality (1.8%, 3.2%, and 6%, p = 0.07), lower heart failure (1.8%, 4.3%, and 7.8%, p <0.001), and MACE (5.1%, 9.6%, and 16.1%, p = 0.001) at 30 days compared to groups B and C, respectively. The rate of MACE at 1 year was 7.6%, 17.1%, and 20.2% in groups A, B, and C, respectively (p <0.001). Immediate STR independently predicted MACE (adjusted hazard ratio 0.36, 95% confidence interval 0.21 to 0.61, p = 0.001, group A vs C), and STR at 90 minutes did not. In conclusion, STR analysis performed immediately after PPCI provided superior differentiation for adverse cardiovascular events compared to STR at 90 minutes. Immediate STR should be the contemporary goal of reperfusion with PPCI.