Background: Ischemic postconditioning (IPost) during primary percutaneous coronary intervention (PPCI) is suggested to reduce myocardial damage. However, the association with ST-segment resolution (STR) and clinical outcome is not determined. The primary aim of this study was to evaluate the association of IPost with STR and clinical outcome. Secondly, we sought to determine the relationship between STR and cardiac magnetic resonance (CMR) parameters in these patients. Methods: One hundred eighteen patients referred for PPCI were randomly assigned to either conventional PPCI or PPCI with IPost. In a single electrocardiographic lead, STR was determined. Treatment modalities were compared as regards STR, ST-segment elevation, and the number of patients achieving complete-STR (≥70%), incomplete-STR (30%-70%), and no-STR (<30%). Patients were evaluated for clinical outcome after 15 months. Furthermore, patients with and without complete-STR were compared as regards CMR parameters. Results: There was a tendency toward a better outcome with IPost for the number of patients achieving complete-STR (55% vs 63%; P = .09), ST-segment elevation (1.41 vs 1.12 mm; P = .07), and New York Heart Association class (P = .06). No difference in other cardiac events was observed. Furthermore, data determine that patients with complete-STR have smaller infarct size (12.9% vs 21.1%; P < .01) and a better ejection fraction (55.7% vs 47.7%; P < .01). Conclusions: Patients treated with IPost are suggested to have improved STR and New York Heart Association classification. Infarct size and the functional CMR parameters were better in the patients with complete-STR; as to this, single-lead STR remains an important predictor for successful treatment in patients treated with IPost.