Background Suboptimal myocardial reperfusion is common in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Furthermore, it results in increased infarct size and mortality rates. We performed a meta-analysis to evaluate the role of aspiration thrombectomy (AT) combined with intracoronary administration of glycoprotein IIb/IIIa inhibitors (GPI) in the improvement of myocardial reperfusion and clinical outcomes. Methods PubMed, Embase, Web of Science, and CENTRAL databases were searched for randomized controlled trials (RCTs) investigating combined AT and intracoronary GPI treatment versus AT alone. Outcomes of interest were thrombolysis in myocardial infarction myocardial perfusion grade (TMPG), infarct size (IS) assessed by cardiac magnetic resonance imaging, left ventricular ejection fraction (LVEF), major adverse cardiac events (MACE) at short-term (≤ 1 month) and long-term (6?12 months) follow-up, and bleeding complications during the hospital stay. Results Eight trials involving 923 patients were included. Compared with AT alone, combined AT and intracoronary GPI significantly increased TMPG 3 flow (RR: 1.15, 95% CI: 1.04 to 1.26), reduced IS [mean difference (MD): ?3.46, 95% CI ?5.18 to ?1.73], and improved LVEF (MD: 1.44, 95% CI: 0.54 to 2.33). Furthermore, GPI use decreased the risk of MACE at long-term follow-up (RR: 0.60, 95% CI: 0.37 to 0.98). There was no significant difference between the two groups in the incidence of minor and major bleeding complications. Conclusions Our findings showed that compared with AT alone, combined AT and intracoronary GPI treatment resulted in improved myocardial reperfusion, better cardiac function, and MACE-free survival benefits at the long-term follow-up for patients with STEMI undergoing PPCI.