Secondary prevention after an acute coronary syndrome (ACS) hospitalization is critical to prevent additional morbidity and mortality. While poor adherence to prescribed cardio-protective medications is a known problem;1;2 it is unknown whether an ACS event might motivate patients to achieve better adherence. In a large integrated health care population; we examined initiation and adherence to newly prescribed cardio-protective medications among post-ACS event patients compared to patients who were prescribed these same medications in usual care.Strengths of this study include the large cohort with 12–15 months of follow-up and a robust adherence methodology based on pharmacy dispensing records in this closed health care system. We did not assess adherence to aspirin, an essential medication for this patient population, because it is often obtained over-the-counter and thus not reliably measurable from pharmacy dispensing.Adherence to newly prescribed cardio-protective medications was excellent among ACS patients discharged from the hospital, and substantially better than patients prescribed the same medications in usual care, suggesting that experiencing an ACS event may motivate patients to be more adherent to medications prescribed at discharge than they might be in usual care. However, despite having had an ACS event, and although better adherence than a similar, previously reported study,4 adherence over time among ACS patients remained suboptimal.Our study in a large real world contemporary population illustrates that post-ACS medication adherence was much better than that observed among patients receiving the same medications in usual care, perhaps due to motivation conferred by the ACS event itself. Nonetheless, medication adherence was suboptimal even in ACS patients, limiting the potential benefits of these proven treatments. Multifactorial interventions that address the various psychosocial, socioeconomic, and behavioral patient barriers are needed to improve adherence in these high-risk patients.