OBJECTIVES: Medication non-adherence is associated with worsening health outcomes and higher medical costs.  This study assessed the impact of a prescriber mailing intervention on adherence among 802,355 members enrolled in Medicare Part D prescription drug plans offered by a pharmacy benefit manager. METHODS: Non-adherent members in three drug classes – oral antidiabetics, statins and one class of antihypertensives (RAS antagonists) – were identified if their specific drug class proportion of days covered (PDC) was < 80% in a 12-month baseline period (2010Q4-2011Q3). Letters were mailed to their prescribers suggesting they discuss potential adherence barriers with their patients. Post-mailing PDC was calculated during a 12-month follow-up period after the mailing date. Members were included if they were age 18+, had 2 or more fills within the drug class, and were continuously enrolled in the prescription drug plan during the baseline and follow-up periods. A historical control cohort was constructed using the same eligibility criteria as applied to the intervention cohort but no letter was mailed to the prescribing physicians. Multivariate logistic regression was used to model post-mailing adherence (PDC≥80%), adjusting for age, gender, zip code level income, education and race variables. Analyses were conducted separately for each drug class. RESULTS: Final analyzable members included 21,044 (Intervention=10,707; Control=10,337) for antidiabetics,   106,829 (Intervention=53,957; Control=52,872) for statins, and 73,560 (Intervention=36,706; Control=36,854) for RAS antagonists. The baseline PDCs between the intervention and control cohorts were not statistically different for all the three drug cohorts. Adjusted logistic regression results indicate the prescriber mailing was associated with significant adherence improvement, odds ratio (OR)  1.11 (95% confidence interval [CI], 1.05-1.18), OR 1.16 (95% CI, 1.13-1.19), and OR 1.07 (95% CI, 1.03-1.10) within the antidiabetic, statin and RAS antagonist drug classes, respectively. CONCLUSIONS: Health plans should consider utilizing prescriber mailings in efforts to improve medication adherence for chronic diseases.