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Transradial access (TRA) decreased bleeding after coronary interventions compared with femoral access (FA). However, no large study focused on arterial access-related outcomes in patients with acute coronary syndromes, although procedure-related bleeding significantly impaired prognosis. The aim was to evaluate access site-related outcomes of patients who underwent an invasive coronary procedure in the PRESTO-ACS Study. The cumulative primary study end point was death or reinfarction during hospitalization and at 1-year follow-up. Secondary end points were in-hospital bleeding and a net clinical outcome (combination of the primary end point and bleeding). Of 1,170 patients studied, 863 underwent a percutaneous coronary procedure using FA, and 307, using TRA. Compared with FA, TRA was associated with higher glycoprotein IIb/IIIa inhibitor use (52% vs 34%; p <0.0001). The in-hospital primary end point was similar between TRA (2.6%) and FA (2.9%; p = 0.79). However, TRA was associated with a significant decrease in bleeding (0.7% vs 2.4%; p = 0.05) and a nonsignificant decrease in net clinical outcome (3.3% vs 4.6%; p = 0.30). At 1-year follow-up, the TRA group had a statistically significant decrease in death or reinfarction (4.9% vs 8.3%; p = 0.05), bleeding (0.7% vs 2.7%; p = 0.03), and net clinical outcome (5.5% vs 9.9%; p = 0.02). In conclusion, in patients with non-ST-elevation acute coronary syndromes, use of TRA was associated with lower bleeding complications and identified patients with better long-term outcomes.