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Introduction: Having diabetes is a major contributor to the likelihood of developing and experiencing complications from coronary artery disease. Acute myocardial infarction patients treated with intravenous streptokinase have a lower risk of death and improved survival. The goal of treating ST-elevation myocardial infarction (STEMI) with streptokinase therapy is to stop the infarction process and fix ischemia-metabolic imbalances in viable cells to keep them from dying. Objectives: The objectives of this study were to determine the overall successfulness of streptokinase therapy in all STEMI patients, compare streptokinase therapy successfulness regarding diabetic status among STEMI patients, and explain any related factors causing failure of streptokinase therapy. Method: This cross-sectional research was carried out at Khyber Teaching Hospital's cardiology department in Peshawar, Pakistan. 151 individuals hospitalized with STEMI who were candidates for streptokinase therapy were studied between June 1st, 2022 and September 30th, 2022 (4 months), in which a total of 76 patients had diabetes, whereas the other patients did not. Streptokinase was administered to every single patient. Then, streptokinase therapy outcomes were assessed. Results: Overall successfulness of streptokinase therapy was 86.8% in all STEMI patients. While streptokinase therapy successfulness regarding diabetic status among STEMI patients, streptokinase therapy was more successful in non-diabetic as compared to diabetic patients (97.3% vs. 76.3%) with a p value of <0.0001. These findings show a statistically significant difference in streptokinase therapy success rates between diabetic and non-diabetic patients. Streptokinase therapy failed in diabetic patients due to increased platelet reactivity, delayed hospital presentation due to diminished perception of myocardial ischemia pain, and the presence of diffuse, numerous, small vascular diseases, all of which are unresponsive to treatment. Conclusion: STEMI patients treated with streptokinase had an overall 86.8% success rate. When comparing how well streptokinase therapy worked for diabetic and non-diabetic patients, the results of this study shows that streptokinase therapy was more successful in non-diabetic as compared to diabetic patients. Recommendation: Patients who experience chest pain should be transported to the hospital within 60 minutes. People should be educated about this utilizing social media and flexes in hospitals and public places. Well-trained staff and streptokinase must be available in hospitals. Streptokinase therapy is beneficial for STEMI patients, however many diabetic patients do not achieve complete reperfusion. Therefore, diabetic patients who have experienced a myocardial infarction require specialized care and it highlights the need for increased research into identification of other pharmacological medicines that can reduce this failure rate.