Acute occlusive thrombosis of the coronary artery is the principal cause of myocardial infarction where platelets play an important role. Large size platelets, easily measured by mean platelets volume (MPV) are thrombogenic and commonly seen after ST-segment elevation myocardial infarction (STEMI). ST segment resolution has been shown as a simple non-invasive marker that reflects both epicardial and myocardial reperfusion following thrombolysis. The present study intended to investigate whether MPV on admission correlated with ST segment resolution following thrombolysis in STEMI patient. This cross-sectional analytical study was conducted in the department of cardiology, Mymensingh Medical College and Hospital (MMCH), Mymensingh, Bangladesh from December, 2016 to June, 2018. Total 284 patients with first attack of STEMI were included after considering inclusion and exclusion criteria. Sample population was divided into two groups, Group I – Patients with successful ST segment resolution (≥50%). Group II – Patients with impaired ST segment resolution (<50%). MPV on admission was estimated during estimation of Complete Blood Count (CBC) by Automated Haematology Analyzer & compared between two groups. Successful ST segment resolution (≥50%) was seen in 67% of patients after thrombolysis. Admission MPV was higher in patients with impaired ST segment resolution (<50%) group than patients with ≥50% ST-segment resolution group (12.42±0.89fl vs.10.35±0.77fl respectively, p=0.001). Statistically significant strong negative correlation between MPV and ST segment resolution percentage (r = -0.742, p=0.001) suggesting that the higher the level of MPV, the lower the ST segment resolution percentage in first attack of STEMI patients. Multivariate regression analysis found MPV level on admission as an independent predictor of ST segment resolution. The study concluded that high MPV on admission correlate with impaired ST segment resolution following thrombolysis in STEMI patients.