Background: Abciximab is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been questioned. Preliminary studies suggest that IC-bolus is superior, probably due to high local concentration. In this study, we assess the short-term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI. Methods: In 2006-2008, we randomized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion. Primary end-points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end-points were bleeding complications. Results: The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end-point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). Conclusion: IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus. (J Interven Cardiol 2011;24:105-111).