BACKGROUND: Randomized trials have established efficacy of clopidogrel in various types of acute coronary syndromes (ACS). The objective of this study was to examine the temporal trends and patterns of early clopidogrel use (within the first 24 hours of hospitalization) across the spectrum of patients with ACS in Canada. METHODS: Using the multinational, prospective GRACE (Global Registry of Acute Coronary Events) and GRACE(2), we identified 11,177 patients who were admitted for ACS from January 2003 to December 2007 in Canada. Demographic information, clinical features, and treatment were recorded. We examined the early use of clopidogrel over time and in relation to the type of ACS, clinical features on presentation, and the mode of reperfusion therapy. RESULTS: Of the 11,177 patients with ACS, 3,091 (27.7%) had ST-elevation myocardial infarction (STEMI), 5,194 (46.5%) had non-STEMI, and 2,892 (25.9%) had unstable angina; the rates of early clopidogrel administration were 63.0%, 66.6%, and 57.2%, respectively (P < .001). Overall, there was a significant increase in clopidogrel use over the period studied (P for trend < .001). In patients with non-ST-elevation ACS (non-STEMI and unstable angina), clopidogrel use was higher among those with positive cardiac biomarkers compared to those without (67.1% vs 59.8%, P < .001) but similar in the groups with and without ST deviation. There was an inverse relationship between GRACE risk score and rates of early clopidogrel administration. In patients with STEMI receiving fibrinolytic therapy, only 55.7% of patients <65 years old received clopidogrel compared with 47.0% and 42.6% of patients 65 to 74 and >75 years old, respectively (P for trend < .001). CONCLUSIONS: Although early use of clopidogrel therapy has increased over time across the spectrum of ACS, a significant proportion of eligible patients still do not receive this evidence-based therapy. There is a need to optimize the use of proven antiplatelet therapies to improve clinical outcome.