Microvascular obstruction (MVO) is an important and independent determinant of post-infarct remodeling. Fifty-two patients with a successfully reperfused ST-segment elevation acute myocardial infarction (MI) were studied with MRI in the first week and at 4 months post-infarction. On early (i.e., 2–5 min) post-contrast MRI, MVO was detected in 32 patients with an MVO to infarct ratio of 36.3 ± 24.9%. On late (i.e., 10–25 min) post-contrast MRI, MVO was detected in only 27 patients, with an MVO to infarct ratio of 15.9 ± 13.9%. MVO infarcts (n = 32) were associated with higher cardiac enzymes (troponin I, P = 0.016), and lower pre-revascularization thrombolysis in myocardial infarction (TIMI) flow (P = 0.018) than non-MVO infarcts (n = 20). Infarct size was larger in MVO infarcts (25.0 ± 14.3 g) than non-MVO infarcts (12.5 ± 7.9 g), P = 0.0007. Systolic wall thickening in the infarct and peri-infarct area, and left ventricular (LV) ejection fraction (EF) were worse in MVO (46.1 ± 7.2%) than non-MVO infarcts (50.5 ± 6.6%, P = 0.038). At 4 months, MVO infarcts showed more adverse remodeling and lack of functional improvement, whereas non-MVO infarcts improved significantly (LV EF at 4 months, MVO, 47.5 ± 7.8%, P = 0.31; non-MVO, 55.2 ± 10.3%, P = 0.0028). In the majority of patients with successfully reperfused ST-segment elevation MI, MVO is observed, whose present and maximal extent can be best evaluated on early post-contrast MRI. Presence of MVO is associated with more extensive infarctions, and characterized by greater adverse LV remodeling and lack of functional recovery.