Background: Although current guidelines recommend early initiation of clopidogrel in patients with non-ST-segment elevation myocardial infarction (NSTEMI), the degree to which it has been adopted in clinical practice remains unclear. We sought to determine patterns of early (<24 hours of arrival) clopidogrel use and its association with clinical outcomes in patients with NSTEMI not undergoing early percutaneous intervention (PCI). Methods: Using data from the CRUSADE initiative, after the exclusion of patients who underwent PCI within 24 hours of arrival, we studied trends in early clopidogrel use among 93,045 patients with NSTEMI. Multivariable logistic regression models were used to determine the association between early clopidogrel treatment and inhospital outcomes. Results: A total of 38.6% of the NSTEMI patients not undergoing PCI within 24 hours of arrival received early clopidogrel. Adjusted inhospital mortality rate was lower in the early clopidogrel group compared to the group that did not receive it on admission (odds ratio 0.68, 95% CI 0.61-0.77). The rate of major bleeding in patients not undergoing coronary artery bypass surgery was similar among the groups treated with and without early clopidogrel (9.5% vs 9.5%, P = .90). Conclusions: Until recently, up to 50% of NSTEMI patients in contemporary practice in the United States not undergoing PCI within 24 hours of arrival in the United States are not treated according to guideline recommendations. Among a high-risk NSTEMI population not undergoing PCI within 24 hours of arrival, the nonrandomized short-term use of clopidogrel is associated with a lower risk of inhospital mortality without an increased risk of major bleeding.