OBJECTIVES: The recent ACC/AHA guidelines recommend the use of clopidogrel for at least 1 year in ACS-PCI patients who are not at high risk of bleeding. However, use of clopidogrel may not meet this guidance due to compliance issues.  In this study, 1-year compliance of clopidogrel by ACS patients with or without diabetes mellitus (DM) was studied. METHODS: A total of N=12,502 ACS patients, aged 18-64 years and hospitalized with a primary diagnosis of ACS between January 1, 2005 and December 31, 2006 were identified with complete 1-year follow-up eligibility and drug use information in the MarketScan claims database. Patients were categorized into two cohorts: DM (N=3040) and non-DM (N=9462).  Adherence was measured by the medication possession ratio (MPR). Persistence was reported using the time from index hospitalization to the first gap of >30 days between exhausting the supplied medication and filling the next prescription. Adherence and persistence between cohorts was compared using propensity score-adjusted bootstrapping method.  RESULTS: A total of 72.1% (2193/3040) DM patients and 76.1% (7197/9462, p<0.01) non-DM patients had at least 1 outpatient fill for clopidogrel in the 1-year after the index hospitalization.  Among the clopidogrel users (64.9% PCI, 30.8% medical management, 4.3% CABG), the average MPR was 0.78 for DM patients and 0.80 for non-DM patients (p=0.189).  Significantly lower persistence was observed for DM patients vs. non-DM patients (257.6 vs. 274.7 days, p=0.012). ACS patients undergoing PCI had significantly higher persistence compared to medical management patients (280.7 vs. 231.4 days, p<0.001 for DM; 285.7 vs. 254.6 days, p<0.001 for non-DM). CONCLUSIONS: Approximately three-fourths of patients in this study had used clopidogrel after being hospitalized for ACS.  ACS patients with prior diabetic history were less likely to be persistent with medication than non-diabetic ACS patients. This finding might have clinical consequences since DM patients typically have higher risk of cardiac events.