Background: The preferred therapy for people with ST-elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PPCI). Pharmaco-invasive therapy, which can be described as the combination of fibrinolytic therapy followed by angiography with or without PCI, either immediately when there is failed fibrinolysis or within 24 hours in case of successful fibrinolysis, is another technique for treating STEMI patients. Objective: The aim of this study was to compare the effects of pharmaco-invasive strategy on infarct-related artery (IRA) patency and on left ventricular systolic and diastolic functions with those of primary angioplasty in STEMI patients assessed in-hospital before patient discharge. Subjects and methods: This prospective cohort cross-sectional nonrandomized study included a total of 100 patients with 1st attack of acute STEMI who had symptom onset within 12 h, attending at Department of Cardiology, Zagazig University Hospital, Zagazig, Egypt. The patients were randomized into 2 groups (50 patients each), First group underwent PPCI, and the second group underwent pharmaco-invasive PCI. Assessment of myocardial blush grade, global longitudinal strain, and E/e` ratio was done for both groups. Results: The mean age of the study population was 52.95 ± 8.41 with 54 % of the whole population being males. There was a statistically significant difference between the two groups regarding pain to ECG time with a P value of 0.03. The Myocardial blush grade was significantly higher in the Pharmaco-invasive arm with a statistically significant difference between the two groups with P value 0.03. After revascularization there was a better improvement in the diastolic function in the PHINV arm as assessed by E/e` with a P value of 0.004. Conclusion: It could be concluded that pharmaco-invasive strategy could offer a superior outcome regarding the recovery of the diastolic function and a higher myocardial blush grade (which indicates a better microvascular circulation) in STEMI patients compared to those who underwent PPCI.