Objectives: To compare the in-hospital outcome and complications with and without reperfusion therapy with streptokinase among patients with myocardial infarction was the objective of this study. Study Design: Prospective study. Setting: Cardiology Department, Divisional Headquarter Teaching, Hospital, Sargodha. Period: March 2018 to December 2018. Material & Methods: Three hundred (300) patients with acute STEMI of either gender and above 20 years of age, were divided into two groups (180 patients received SK and 120 patients didn’t receive SK. Demographic features, history and physical examination were noted. In hospital mortality and complications were recorded and compared between groups by chi-square test. Results: There were 76.0% male and 24.0% females with mean age of 55.61±11.35 years. Family history of IHD was present in 28.34% patients and 35.0% patients were smoker. Commonest co-morbidity was hypertension (73.34%), followed by diabetes mellitus (36.67%). In-hospital mortality was 6.6% in SK group and 31.6% in non-SK group (p= <0.001). Overall, in-hospital mortality was 16.67%. LVF was 8.33% and 23.33% (p= <0.001), Mitral regurgitation 1.11% and 2.5% (p=0.848), VT/VF 3.33% and 5.83% (p=0.297), Complete heart block 2.22% and 5.83% (p=0.103), Atrial fibrillation 0.55% and 1.67% (p=0.343), Post MI angina 3.33% and 13.33% (p=0.001), Re-infarction 1.11% and 3.33% (p=0.178), CVA 0.0.55% and 0.0% (p=0.812), Ventral septal defect 0.0% and 3.33% (p=0.029) and Hypotension was 25% and 8.33% (p=0.001)in SK and non SK groups, respectively. Conclusions: Reperfusion therapy with streptokinase among patients with myocardial infarction was found effective in terms of significant low in-hospital mortality rate and low complication rate.