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BACKGROUND:: Medications are an integral component of management for many chronic conditions, and suboptimal adherence limits medication effectiveness among persons with multiple chronic conditions (MCC). Medical homes may provide a mechanism for increasing adherence among persons with MCC, thereby enhancing management of chronic conditions. OBJECTIVE:: To examine the association between medical home enrollment and adherence to newly initiated medications among Medicaid enrollees with MCC. RESEARCH DESIGN:: Retrospective cohort study comparing Community Care of North Carolina medical home enrollees to nonenrollees using merged North Carolina Medicaid claims data (fiscal years 2008-2010). SUBJECTS:: Among North Carolina Medicaid-enrolled adults with MCC, we created separate longitudinal cohorts of new users of antidepressants (N=9303), antihypertensive agents (N=12,595), oral diabetic agents (N=6409), and statins (N=9263). MEASURES:: Outcomes were the proportion of days covered (PDC) on treatment medication each month for 12 months and a dichotomous measure of adherence (PDC>0.80). Our primary analysis utilized person-level fixed effects models. Sensitivity analyses included propensity score and person-level random-effect models. RESULTS:: Compared with nonenrollees, medical home enrollees exhibited higher PDC by 4.7, 6.0, 4.8, and 5.1 percentage points for depression, hypertension, diabetes, and hyperlipidemia, respectively (P's<0.001). The dichotomous adherence measure showed similar increases, with absolute differences of 4.1, 4.5, 3.5, and 4.6 percentage points, respectively (P's<0.001). CONCLUSIONS:: Among Medicaid enrollees with MCC, adherence to new medications is greater for those enrolled in medical homes