To estimate patient adherence with once-a-day (QD) vs. twice-a-day (BID) chronic medications following hospital discharge for ACS. A retrospective cohort study of patients discharged between 1/1/2007 and 4/30/2009 with an ACS diagnosis was performed using a large hospital and pharmacy claims dataset. Two chronic medications dispensed for QD and BID utilization, carvedilol and metformin, were analyzed for adherence measures [persistency, days on therapy, compliance (medication possession ratio, MPR), total # of dispensed prescriptions, gap (days) between refills] over a 12 month post-index period. Included patients had first dispensed prescription of carvedilol or metformin within 60 days of discharge (index prescription) and had Rx activity for any drug ≥ 12 months post-index. Persistence was defined as percentage of patients without a therapy lapse of > 30 days from last dispensed day's supply. Persistency with carvedilol QD vs. BID (N=168 vs. 2086) at 6 months was 44.0% vs 43.7% and at 12 months was 24.4% vs. 25.5%. Persistency with metformin QD vs. BID (N=136 vs. 614) at 6 months was 50.7% vs 53.7% and at 12 months was 28.7 vs. 35.0%. The average days on therapy for carvedilol QD vs. BID at 6 months was 120.5 vs. 121.9 and at 12 months was 196.7 vs. 203.0. Average days on therapy for metformin QD vs. BID at 6 months was 123.6 vs. 136.2 and at 12 months was 206.1 vs. 237.7. Compliance (MPR) with QD vs. BID carvedilol at 12 months was 84.2% vs 80.7% and for metformin was 77.6% vs 81.6%. Additional adherence metrics were consistent for QD vs. BID dosing. In ACS patients, no clinically meaningful differences on adherence measures were observed between QD versus BID dosing formulations over a 12 month follow-up period. Results indicate potential opportunities to improve persistency with chronic therapies in ACS patients.