In the pathogenesis of atherosclerosis, oxidative stress plays a major role in plaque instability, rupture, and erosion, which subsequently leads to thrombus formation and causes total infarct-related artery (IRA) occlusion. We investigated the relationship between spontaneous reperfusion (SR) of IRA and oxidative stress in patients with anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. A total of 341 consecutive patients with anterior STEMI were prospectively included in the present study. Patients were divided into 2 groups according to their thrombolysis in myocardial infarction (TIMI) flow grade: SR group (66 patients, TIMI flow 3) and non-SR group (275 patients, TIMI flow 0-2). On multivariate logistic regression analysis, oxidative stress index ( = 0.868, 95% confidence interval [CI] = 0.806-0.934, P < .001), neutrophil to lymphocyte ratio, uric acid, mean platelet volume, Killip 2 to 4 class, and initial SYNTAX score were independently associated with SR. Oxidative stress as well as inflammation may play a pivotal role in the pathogenesis of SR in patients with STEMI.