Abstract Background Primary percutaneous coronary intervention (PPCI) may be complicated by intracoronary thrombus accumulation in ST elevation myocardial infarction (STEMI) leading to decrease in myocardial perfusion and increase in infarct size. The utilization of aspiration thrombectomy and intracoronary tirofiban in STEMI patients undergoing PPCI hold clinical relevance by removal of thrombus burden, potentially reducing distal embolization and improving myocardial perfusion and by targeting platelet aggregation to mitigate thrombotic complications, respectively. Given the paramount importance of achieving rapid and effective reperfusion in STEMI, the evaluation of these interventions is warranted to assess overall impact on patient outcomes in terms of safety and efficacy. Purpose The current meta-analysis aims to investigate the clinical outcomes of aspiration thrombectomy (AT) with intracoronary tirofiban versus AT alone during PPCI. Methods A systematic search for randomized controlled trials that evaluate the safety and efficacy of aspiration thrombectomy with intracoronary tirofiban in STEMI patients who underwent PPCI was done using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 and involved human subjects. Search terms included "Aspiration Thrombectomy", "Intracoronary Tirofiban", "Primary Percutaneous Coronary Intervention" and "STEMI patients". Results Four RCTs (n: 490 participants) were included in this meta-analysis comparing aspiration thrombectomy with intracoronary tirofiban versus aspiration thrombectomy alone in STEMI patients undergoing PPCI. The results revealed no statistically significant difference in ST segment resolution (RR 1.02, 95%, CI: 0.97 - 1.08, P = 0.41, I2 = 0%), myocardial blush grade 2-3, (risk ratio of 1.04, 95%, CI: 0.97 – 1.12, P = 0.22, I2 = 62%) and TIMI 3 flow (risk ratio of 1.0, 95% CI: 0.95 - 1.04, P = 0.87). The occurrence of major adverse cardiovascular events did not significantly differ between the two groups (RR 0.46, 95% CI: 0.19 – 1.09, P = 0.08, I2 = 0%). There was no statistically significant difference in terms of bleeding when combining intracoronary tirofiban to standard medical therapy (RR 1.35, 95% CI: 0.64 – 2.84, P= 0.78, 4 trials [490 patients]). Conclusion In primary percutaneous coronary intervention, MACE outcomes of aspiration thrombectomy with intracoronary tirofiban were similar to that for aspiration thrombectomy alone in terms of improving myocardial perfusion in STEMI patients without increasing the risk for bleeding. Our meta-analysis suggests that AT alone may be the more acceptable standard during PPCI when encountering heavy thrombus burden. Future validated studies may help further investigate the strategy of adding tirofiban during aspiration thrombectomy.1. Primary Outcomes2. Secondary Outcomes