OBJECTIVES: To evaluate medication adherence and persistence in patients with acute coronary syndromes (ACS) who initiated prasugrel following a percutaneous coronary intervention (PCI). METHODS: We identified adult patients with no prior stroke/transient ischemic attack who filled prasugrel as their first dispensed outpatient thienopyridine within 30 days post ACS-PCI discharge from July 10, 2009 to June 30, 2010 using claims from the Thomson Reuters Marketscan dataset. Baseline characteristics were assessed in the 6 months prior to the index hospitalization, and patients were required to have ≥12 months of continuous enrollment post-discharge. Predictors of adherence ≥80%, calculated using the medication possession ratio (MPR) during the 12-month follow-up period, were identified using a logistic regression model. Persistence was assessed with survival analysis techniques using a ≥15-day gap to define a discontinuation. A Cox proportional hazards model identified predictors of prasugrel discontinuation. RESULTS: The cohort was composed of 1340 patients with a mean age of 56.3 years; 79.5% were male. The average MPR was 0.79 and nearly 70% of patients had adherence ≥80%. Patients with prior statin use had higher odds of adherence (OR: 1.59, 95% CI: 1.22-2.09). Coagulation defects (OR: 0.13, 95% CI: 0.03-0.52), baseline depression (OR: 0.33, 95% CI: 0.14-0.75), history of bleeding (OR: 0.44, 95% CI: 0.20-0.95), prior PCI (OR: 0.61, 95% CI: 0.39-0.94), and prior clopidogrel use (OR: 0.68, 95% CI: 0.46-1.00) were associated with decreased odds of adherence. The median time to prasugrel discontinuation was 242 days. Baseline factors associated with prasugrel discontinuation were prior anemia (HR: 1.65, 95% CI: 1.21-2.25), prior cardiomyopathy (HR: 2.07, 95% CI: 1.02-4.19), and prior deep vein thrombosis (HR: 2.71, 95% CI: 1.00-7.32). CONCLUSIONS: Adherence to prasugrel following ACS-PCI was relatively high. Patients with coagulation defects or depression at baseline had the highest odds of suboptimal adherence. Anemia, prior DVT and cardiomyopathy were among factors associated with prasugrel early discontinuation.