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BACKGROUND P2Y12 antiplatelet therapy (APT) is highly efficacious in reducing the incidence of ischemic events in patients with acute coronary syndrome (ACS); however, it is associated with several adverse complications. Data on P2Y12-associated complications and adherence to APT are sparse. OBJECTIVE To describe the characteristics, frequency of P2Y12-associated complications, adherence and persistence to P2Y12 APT, and health care utilization among ACS patients on P2Y12 APT. METHODS This retrospective observational study of the MarketScan Commercial Claims and Encounters Database identified patients aged ≥ 18 years who were discharged from an ACS hospitalization in 2012-2014 and initiated P2Y12 APT (ticagrelor, prasugrel, or clopidogrel). The proportion of patients within each treatment group who experienced P2Y12-associated complications within 1 year and who were adherent to APT were determined. Frequencies of all-cause health care utilization (i.e., hospitalization, length of stay, emergency room [ER] visits, outpatient visits, cardiac events, and transfusions) were evaluated for each treatment group. Poisson regressions were conducted to evaluate the association between nonad-herence with P2Y12 APT and health care utilization, after adjusting for demographics (age and gender), health insurance type, and comorbidities. RESULTS Among 11,629 ACS patients, most were male; 44.6% had hypertension; 20.6% had diabetes; and 53.4% had hyperlipidemia. Clopidogrel use was common (62.6%), with ticagrelor use less common (9.0%). Among all groups, approximately one third experienced P2Y12-associated complications. One-year adherence to APT was suboptimal (68% overall), with 73.3% adherence among prasugrel users, followed by 71.4% adherence among ticagrelor users and 65.6% adherence among clopidogrel users. Switching was most common with ticagrelor users. Inpatient hospitalizations, cardiac events, and transfusions were more common in clopidogrel users compared with prasugrel and ticagrelor users. Nonadherent patients experienced significantly more hospitalizations, ER visits, and transfusions (1.34, 1.09, and 1.85 [P < 0.05], respectively) compared with adherent patients. These trends of association remained consistent across all treatment groups. Also, patients not adherent to ticagrelor experienced 1.9 times as many cardiac events as adherent patients. However, this association was not significant for clopidogrel and prasugrel users. Patients not adherent to P2Y12 APT experienced significantly lower outpatient visits compared with adherent patients. CONCLUSIONS Complications associated with P2Y12 in ACS patients treated with P2Y12 APT were common, with dyspnea, heart block, and major or life-threatening bleeding as the most common. Adherence was significantly associated with lower health care utilization. Increased adherence to secondary prevention therapy among these very high-risk patients is crucial. Disease management strategies to improve adherence and reduce treatment-associated adverse events through individualized patient care, alternative secondary treatment options, and physician awareness should be designed, implemented, and sustained. DISCLOSURES Data analysis was conducted by Merck & Co., the manufacturer of vorapaxar (ZONTIVITY). At the time of this study, Vyas was an employee of Rutgers University, which received grant funding from Merck & Co. for this study, and is now employed with the University of Rhode Island. Patel was employed by Symphony Solutions and the University of North Carolina during the drafting and revising of the manuscript. Bash is employed by Merck & Co. Simpson received consulting fees from Merck & Co. for work on this study and has received fees for research from Amgen and Pfizer. Study concept and design were contributed by Vyas, Bash, Patel, and Simpson. Patel took the lead in data collection, assisted by the other authors. All the authors contributed equally to data analysis and manuscript preparation. The abstract for this study was presented as a poster at the American Heart Association Scientific Sessions 2016; November 12-16, 2016; New Orleans, Louisiana.