Recent studies have suggested that low-dose aspirin has preserved benefit with less bleeding compared with standard-dose aspirin when given with or without clopidogrel in patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACSs). We evaluated 22,618 patients with NSTE ACSs and high-risk features (ischemic ST-segment changes and/or positive cardiac markers) from 369 hospitals included in the CRUSADE initiative from May 4, 2003 to September 30, 2004. We analyzed acute (<24 hours of admission) and discharge aspirin doses in relation to concomitant clopidogrel use and other clinical predictors. Dosing of aspirin in the first 24 hours was as follows: 17.3% of patients (n = 3,911) received 81 mg, 13.5% (n = 3,062) received 162 mg, 67.4% (n = 15,247) received 325 mg, and 1.8% (n = 398) received >325 mg. Use of lower dose aspirin increased at discharge: 40.2% (n = 7,524) received 81 mg, 3.1% (n = 579) received 162 mg, and 55.7% (n = 10,423) received 325 mg. In patients who received concomitant clopidogrel at discharge (n = 12,635), 37.6% received aspirin 81 mg and 58.5% received 325 mg. Compared with patients who did not receive concomitant discharge clopidogrel (n = 4,772), 44.0% received aspirin 81 mg and 51.2% received 325 mg. Use of aspirin 81 mg was significantly lower in patients undergoing percutaneous coronary intervention (31.5% vs 46.2%, p <0.0001). In conclusion, most patients with high-risk NSTE ACSs in the United States continue to be treated with aspirin 325 mg at discharge with and without concomitant clopidogrel, despite recent studies that have shown a better safety profile with low-dose aspirin.