Background: Reperfusion injury might be considered as the consequence of insufficient perfusion due to fibrin and fibrinogen deposition in the microvasculature. Therefore, streptokinase, being a fibrinolytic drug, injected in the culprit artery immediately after primary PCI can be a suitable solution for achieving better myocardial perfusion. Aim of study: To assess the impact of complementary low dose intracoronary streptokinase (ICSK) administration immediately after primary PCI on left ventricular functions. Patients and methods: This double blinded randomized controlled clinical trial included 64 patients within 12 h of presentation by first STEMI who were candidate for primary percutaneous coronary intervention (PPCI). They were randomized equally to 2 groups. Immediately after primary PCI the first group received 250 kU ICSK vs placebo in the second group. Evaluation of LV functions was done by comparing the baseline echocardiographic parameters including left ventricle (LV) global longitudinal strain (GLS) before and after PPCI. Assessment of ST segment resolution (STR) 90 min after primary PCI, enzymatic infarct size in addition to comparing post-PPCI TIMI flow grade, TIMI frame count (TFC), Myocardial blush grade (MBG) and TIMI myocardial perfusion grade (TMPG) between both groups. Successful reperfusion after PPCI was defined as patients who achieved (TIMI 3 flow, MBG 3, > 70% ST segment resolution) Results: Post-PPCI LV GLS and LVEF were significantly higher in ICSK group (P = 0.005, 0.02 respectively). Post PPCI E/e' was significantly lower in ICSK group (P = 0.007). Peak CK-MB, CK-MB area under the curve (AUC), Troponin-I (72-hr); representing the enzymatic infarct size, were significantly lower in the ICSK group (P = 0.015, < 0.001, < 0.001 respectively). STR > 70% after PPCI was significantly higher in ICSK group (P = 0.045). Post-PPCI TFC was significantly lower in the ICSK group (P = 0.05). Post-PPCI MBG & TMPG were significantly higher in ICSK group (P = 0.04, 0.03 respectively). Multivariate linear regression analysis showed that each of ICSK administration, pain to stent time interval, post-PPCI MBG were independent predictors for LV GLS improvement after PPCI. Multivariate logistic regression analysis showed that the likelihood of achieving successful reperfusion post-PPCI was also associated with ICSK administration [OR= 0.123, 95% CI (0.02 - 0.75), P = 0.024] and was inversely associated with pain to stent time interval [OR= 0.995, 95% CI (0.990-0.999), P = 0.015]. Conclusion: Low-dose ICSK given immediately after primary PCI significantly led to improvement of LV GLS and LVEF, E/e'. It also reduced the enzymatic infarct size and was an independent predictor of successful reperfusion and LV GLS improvement after PPCI.