Background: Oral chemotherapy is increasingly prescribed to treat cancer. Despite benefits such as convenience of use, concerns have been raised regarding adherence to therapy. The objective was to compare and measure rates of adherence and abandonment in patients filling prescriptions in traditional retail versus specialty pharmacy channels. Methods: Using a retrospective cohort design, we selected patients aged ≥18 years with a prescription for erlotinib, capecitabine, or imatinib during 2007-2011 from a Medco population of both U.S. commercial and Medicare health plans. Patients were classified according to the initial oral oncolytic received and the pharmacy channel providing the medication. Abandonment was defined as a reversal following the initial approval of the prescription claim with no additional paid claims for the agent within 90 days of reversal. Adherence was defined as the proportion of days covered between the date of the first and last oral prescription. Patients were classified as adherent if the proportion of days covered was ≥80%. Unadjusted comparisons of adherence and abandonment measures were assessed using chi-square tests. Logistic regression models adjusted for baseline characteristics were used to examine the impact of pharmacy channel on abandonment and adherence. Results: Among patients treated with an oral oncolytic, 15,071 were prescribed erlotinib, 20,062 were prescribed capecitabine and 7,233 were prescribed imatinib. For all study cohorts, Medco specialty channel had the highest proportion of adherent patients compared with traditional retail (erlotinib 84% vs. 80%, capecitabine 63% vs. 35%, and imatinib 72% vs. 67%, P<.001 all comparisons). Abandonment of the initial prescription was low with overall rates of 1.9%, 1.6%, and 1.2% for erlotinib, capecitabine, and imatinib, respectively. In multivariate models, specialty channel was significantly associated with lower abandonment and increased adherence for each cohort. Conclusions: Pharmacy channel appears to be influential on abandonment and adherence. Lower rates of abandonment and higher rates of adherence were observed among specialty pharmacy patients compared with traditional retail.