Microvascular obstruction following percutaneous coronary intervention (PCI) is highly prevalent and independently associated with adverse clinical outcomes. Microvascular obstruction is determined by index of the microvascular resistance. We performed a systematic review with meta-analysis of all published randomized clinical trials (RCTs) studying the effect of intra-coronary thrombolysis with PCI as compared to standard treatment among patients with ST-segment elevated myocardial infarction. We included 6 RCTs summing up to 947 patients in the final analysis. Intra-coronary thrombolysis resulted in significantly lower index of microvascular resistance [standardized mean difference: - 13.74, 95% confidence interval (CI): - 16.74 to - 10.73, P value < 0.001, I2 = 0%]. There was no difference noted in the occurrence of major adverse cardiac events with intra-coronary thrombolysis as compared to standard treatment [Odds ratio: 0.71, 95% CI: 0.46-1.08, P value = 0.11, I2 = 0%]. The absence of heterogeneity deferred us from using dose-response analysis to account for altering dose used across studies. The results of the present meta-analysis highlights the role of intra-coronary thrombolysis in reducing microvascular obstruction. No effect of intra-coronary thrombolysis was noted on the occurrence of major adverse cardiac events.