OBJECTIVES: Readmission rates in the US following acute myocardial infarction (AMI) remain high despite intensive medical therapy.  This study evaluated the association between antiplatelet therapy, aspirin ± clopidogrel and the short and long term readmission rates in patients who were hospitalized for AMI. METHODS: Patients with an index hospitalization for AMI in 2007–2009 and also received in-hospital aspirin ± clopidogrel were selected based on diagnoses and pharmacy records from 122 hospitals in a US electronic medical record database (Cerner's Health Facts).  Readmission for any reason or recurrent AMI within 30 days and 1 year following index AMI discharge was assessed based on hospital records.  Multivariate logistic regression was used to estimate the association between readmission and in-hospital antiplatelet therapy, adjusted for age, gender, comorbidities, AMI type, and coronary revascularization during index hospitalization. RESULTS: Among 23,394 patients diagnosed with AMI during index hospitalization (mean age 68.7 years; 58% male), 35% received aspirin alone and 65% received aspirin + clopidogrel in hospital.  Patients on aspirin + clopidogrel were younger, had more STEMI diagnosis, higher rates for hypertension, dyslipidemia, diabetes, and PCI/stent placement, but lower rates for atrial fibrillation, congestive heart failure, and cerebrovascular disease than patients on aspirin alone (all p<0.001).  Patients who received aspirin + clopidogrel had lower rates of readmission for any reason at 30 days (11.5% vs. 14.7%; adjusted odds ratio (OR) = 0.89 [95% CI: 0.82, 0.97]) and at 1 year (33.2% vs. 37.3%; OR = 1.06 [1.00, 1.13]) compared to aspirin alone.  AMI-related readmission rates were similar between in-hospital treatment regimens. CONCLUSIONS: Both 30-day and 1-year readmission rates remain high post AMI discharge, despite antiplatelet therapy using aspirin ± clopidogrel.  In-hospital dual antiplatelet therapy was associated with a reduction in short-term readmission rate overall but not for long-term or recurrent AMI in this cohort.