OBJECTIVES: Specialty pharmacy programs are increasingly used to improve the quality of outpatient therapy with oral medications for cancer. We evaluated whether use of particular specialty pharmacy services is associated with improved oncology medication use and reduced overall healthcare costs, as compared to retail pharmacy services. METHODS: The study is a retrospective claims analysis post implementation of a specialty pharmacy program, by a national commercial payer. A matched sample of patients assigned to use specialty pharmacies and those who used retail pharmacies for oral cancer therapies were compared. Primary outcomes were financial, including overall health care costs, outpatient costs, medical costs, and pharmacy costs. Outcomes one year post-implementation in specialty pharmacy users and retail pharmacy controls were compared with t-tests for continuous variables, chi-square for nominal variables, and logistic regression for matching. Propensity scores were used to adjust for unmeasured confounding in the groups. RESULTS: The final analysis included 464 patients per cohort. The mean total costs per patient was 13% lower in the specialty pharmacy group ($84,105 vs. $97,196; difference = $-13,092; P = 0.02) in the follow-up period. The mean outpatient hospital costs ($16,777 vs. $28,629, difference = $-11,852; P <0.01) were lower in the specialty group by 41%, with an associated significant difference in outpatient hospital visits (15.75 vs. 19.66, P <0.01). Patients in the specialty pharmacy group were more adherent to therapy, MPR 0.73 vs. 0.66, (P <0.01). CONCLUSIONS: This specialty pharmacy program implemented by a national commercial payer appears to improve oral oncology medication adherence and decrease overall health care costs, mainly by impacting outpatient hospital utilization.