OBJECTIVES: Compare the annual subsequent coronary event rate (ASCER) and associated costs between patients initiating adjunct therapy with either niacin extended-release (NER) for comprehensive lipid panel management or ezetimibe (EZE) for continued LDL-C reduction after an acute coronary event (ACE). METHODS: Patients with an ACE between January 1, 2004 and May 31, 2009 were identified (Index Date was defined as the earliest ACE). Patients age ≥18, ≥6 months eligibility pre- and post-Index Date, ≥1 statin fill and no statin augmenting fill 6 months before the Index Date, and sub-optimal baseline HDL-C (<40 or <50 mg/dL for men and women) or triglyceride (>150 or >200 mg/dL for diabetic and non-diabetic) were included. Cohorts were determined based on NER or EZE fills within 6 months of the Index Date (Cohort ID Period). Patients with alternative lipid agents or coronary event during the Cohort ID Period were excluded.  Outcomes included ASCER and event-related medical costs and were compared via generalized linear models. Multivariate analyses controlled for age, gender, health coverage, geography, co-morbidities, baseline lipids, and severity of initial ACE. RESULTS: A total of 328 patients added NER (n=145) or EZE (n=183) and met all study criteria. NER patients were less likely female (8% vs. 29%, P<0.0001), had lower baseline LDL-C (81±32 vs. 112±40; P<0.0001) and HDL-C (34±7 vs. 40±9; P<0.0001). Age (57±8 vs. 58±10; P=0.2020), Deyo-Charlson comorbidity index (0.6±1.1 vs. 0.9 ±1.4; P=0.0923) and triglycerides (185±118 vs. 199 ±94; P=0.2531) were not statistically different. Compared to EZE, NER patients had a 57% decrease in ASCER (incidence ratio: 0.43, 95%CI: 0.24-0.77). Clinical findings corresponded with 87% reduction in adjusted annual event-related costs compared to EZE (0.13; 95% CI: 0.04 – 0.41). CONCLUSIONS: Among patients requiring lipid management, adopting a comprehensive lipid approach demonstrated lower ASCER compared to further reducing LDL-C, consequently reducing annual event-related medical costs following an ACE.