Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% 45/400 vs 5.3% 21/400; hazard ratio HR, 2.26; 95% confidence interval CI, 1.34 to 3.79; =0.002). The incidences of major bleeding (7.5% 29/400 vs 4.1% 16/400, =0.04) and fatal bleeding (1% 4/400 vs 0%, =0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% 36/400 vs 5.8% 23/400; HR, 1.62; 95% CI, 0.96 to 2.74; =0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.