Background: STEMI patients often require reperfusion therapy to restore blood flow to the affected heart muscle. MPV has been proposed as a potential predictor of reperfusion success in STEMI patients. This study aimed to show correlation between MPV on admission and ST segment resolution following reperfusion therapy in STEMI patients. Methods: This observational, single-center study was conducted on patients with ACS to assess their clinical outcomes and the predictive role of hematological indices, including MPV, in determining the effectiveness of reperfusion therapy, encompassing fibrinolytics and primary PCI. Our study comprised 100 STEMI patients, with 50 undergoing PCI and the remaining 50 receiving thrombolytic therapy. Among the PCI group, 42 patients achieved successful treatment, while in the fibrinolytic group, only 32 cases were successful. 74 patients experienced ST-elevation resolution (Group A), while 26 cases did not exhibit resolution of their ST abnormalities (Group B). Results: ROC curve analysis revealed that MPV-pre at cut-off value of 11.15 could be good predictive test of unsuccessful reperfusion with 76.9% sensitivity and 70.3% specificity (AUC, 0.77 and 95% CI, 0.67-0.87). MPV-post at cut-off value of 10.35 could be excellent predictive test of unsuccessful reperfusion with 80.8% sensitivity and 70.3% specificity (AUC, 0.89 and 95% CI, 0.82-0.96). There is a significant positive correlation between MPV_Pre and MPV_post (r = 0.254, p = 0.011). Conclusion: There is a correlation between MPV on admission and ST segment resolution following reperfusion therapy (in STEMI patients. MPV may be utilized as a prognostic predictor of success of thrombolysis following STEMI.