Microvascular obstruction (MVO) frequently develops after ST-elevation myocardial infarction (STEMI) and is associated with increased mortality and adverse left-ventricular remodeling. We hypothesized that increased extravascular compressive forces in the myocardium that arise from the development of myocardial edema as a consequence of ischemia-reperfusion injury would contribute to the development of MVO. We measured MVO, infarct size and left ventricular mass in STEMI patients (n=385) using cardiac MRI 2-3 days following successful percutaneous coronary intervention and stenting. MVO was found in 57% of STEMI patients. The average infarct size was 45 ± 29 grams. Patients with MVO had significantly greater infarct size and reduced LV function (p < 0.01) compared to patients without MVO. Patients with MVO had significantly greater LV mass than patients without MVO and there was a linear increase in MVO with increasing LV mass (p < 0.001). Myocardial edema by T2-weighted imaging increased with increasing LV mass and patients with MVO had significantly greater myocardial edema than patients without MVO (p < 0.01). Patients with MVO had significantly greater LVEDP than patients without MVO (p < 0.05). In a cohort of STEMI patients who underwent primary percutaneous intervention we observed that MVO increased linearly with increasing LV mass and was associated with increased myocardial edema and higher LVEDP. These observations support the concept that extravascular compressive forces in the left ventricle may increase with increasing ischemic injury and contribute to the development of MVO.