Background: Specialty pharmacy programs are increasingly used to improve the quality of outpatient therapy with oral medications for cancer. We evaluated whether use of specialty pharmacy services is associated with improved medication use and reduced overall healthcare costs, as compared to retail pharmacy services, for specific oral oncology medications. Methods: The study is a retrospective claims analysis after the implementation of a specialty pharmacy program. A matched sample of patients assigned to use specialty pharmacies and those who used retail pharmacies for specific oral cancer therapies were compared. Primary outcomes were financial, including overall healthcare costs, outpatient costs, medical costs, and pharmacy costs. Outcomes one year pre- and 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 v $97,196; difference = $-13,092; P = 0.02) in the follow-up period. The mean outpatient hospital costs ($16,777 v $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 v 19.66, P < 0.01). Patients in the specialty pharmacy group were more adherent to therapy, MPR 0.73 v 0.66, (P < 0.01). A nonsignificant trend of fewer patients started intravenous chemotherapy in the specialty group (7.76% v 12.28%, P = 0.27). Conclusions: Specialty pharmacies appear to improve oral oncology medication adherence and decrease overall healthcare costs, mainly by impacting outpatient hospital utilization.