Objective To systematically review the effectiveness and safety of intracoronary glycoprotein IIb/IIIa inhibitors (GPIs) undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) compared with intravenous administration. Methods Databases including PubMed, EMbase, The Cochrane Library (Issue 9, 2012), Ovid, CBM, CNKI and VIP were electronically searched for randomized controlled trials (RCTs) about intracoronary GPIs administration versus intravenous administration undergoing PCI for ACS from inception to September 30th, 2012. Meanwhile, domestic relevant papers published in recent 1 year were also retrieved manually. References of the included studies were retrieved, too. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data, and assessed the methodologically quality of the included studies. Then, meta-analysis was performed using RevMan 5.1 software. Results 10 RCTs involving 3 553 ACS patients were finally included. The results of meta-analysis showed that: compared with intravenous administration, intracoronary GPIs administration decreased the major adverse cardiovascular event (MACE) (OR=0.54, 95%CI 0.34 to 0.85, P=0.008). The incidences of re-infarction (MI), revascularization (TVR) and heart failure were (OR=0.62, 95%CI 0.39 to 0.97, P=0.04), (OR=0.59, 95%CI 0.36 to 0.97, P=0.04), (OR=0.52, 95%CI 0.32 to 0.84, P=0.008), respectively. But for the mortality, there were no significant differences between the two groups (OR=0.81, 95%CI 0.58 to 1.14, P=0.23). Intravenous administration and intracoronary administration were alike in the incidences of mild/serious bleeding (mild: OR=0.94, 95%CI 0.75 to 1.19, P=0.63; serious: OR=1.18, 95%CI 0.76, 1.84, P=0.47). Conclusion Compared with routine GPIs regimen of intravenous bolus, intracoronary administration with initial dosage showed significant benefits in clinical outcomes in ACS patients undergoing PCI, which could not increase the incidence of bleeding.