Background-Despite early recanalization of an occluded infarct artery, reperfusion at the level of the microcirculation may remain impaired owing to a process of microvascular reperfusion injury. Methods and Results-Microvascular reperfusion injury was studied in 91 patients with acute myocardial infarction (AMI) by evaluation of the resolution of ST-segment elevation after successful PTCA. Impaired microvascular reperfusion, defined as the presence of persistent (greater than or equal to 50% of initial value) ST-segment elevation (ST greater than or equal to 50%) at the end of coronary intervention, was observed in 33 patients (36%) and was independently correlated with low systolic pressure on admission and high age. Patients greater than or equal to 55 years of age with systolic pressures less than or equal to 120 mm Hg were at high risk for development of-impaired reperfusion compared with patients not meeting these criteria (72% versus 14%, P<0.001). Impaired microvascular reperfusion was associated with a more extensive infarction and worse clinical outcome at the I-year follow-up: cardiac death rate, 15% versus 2% (ST greater than or equal to 50% versus ST <50%, P=0.01); nonfatal MI rate, 9% versus 2% (P=0.1); and total major adverse cardiac event (MACE) rate, 45% versus 15% (P<0.005). ST greater than or equal to 50% was the most important independent determinant of MACE with an adjusted risk ratio of 3.4. Conclusions-Impaired microvascular reperfusion, as evidenced by ST greater than or equal to 50% after successful recanalization, occurs in more than one third of our AMI patients, especially in older patients with low systolic pressure. Its detrimental implications on clinical outcome reinforce the need to develop adjunctive agents that attenuate the process of reperfusion injury.