OBJECTIVES: To evaluate whether, compared with retail services, the use of specialty home delivery pharmacy services embedded in a health plan’s operations is associated with improved medication adherence and reduced overall healthcare costs. METHODS: A retrospective, matched cohort study using administrative claims data was conducted using pharmacy and medical claims for patients receiving specialty medication from a specialty home delivery pharmacy and those filling at retail. Based on sample size and potential for differences in outcomes, subpopulations taking inflammatory, multiple sclerosis, oncology, HIV and renal transplant medications were selected. Patients were identified based on their first condition-related medication fill in 2014 and followed for one year. The cohorts were matched on confounders including demographics, Charlson comorbidity score and baseline use of pharmaceutical therapy, as well as condition-specific factors. Statistically significant differences were evaluated using T and chi-squared tests. RESULTS: The final analysis included 3,910 patients per cohort. The mean medical cost per patient was 10.8% lower in the home delivery group ($11,928 v $10,639; difference = $-1,289; P = 0.0176) in the follow-up period. The home delivery group had lower mean inpatient hospital costs ($2,640 v $1,809, difference = $-832; P < .0001). Patients in the home delivery group were more adherent to therapy, 62.9% v 72.1% had PDC > 80%, (P < 0.0001). Further, patients in the home delivery pharmacy group had higher levels of engagement in case management and other disease management programs 22.2% vs 25.2% (P .0019). CONCLUSIONS: After adjusting for measured confounders, individuals who filled their oral and self-injectable specialty medications through mail order pharmacy had higher adherence rates and lower medical cost. This was accompanied by improved engagement in disease/care management programs. These results provide evidence of the effectiveness of patient education, refill management, and clinical management of adverse effects and drug interactions provided by specialty pharmacy services.