Background: Biosimilars provide quality, safe, effective, and lower-cost alternative treatment options that have no difference from their reference product. CVS Health® recently launched a biosimilar adoption strategy to expand access to biosimilars and drive sustainable cost savings and options for consumers. The purpose of this study is to compare treatment duration, adherence, and out-of-pocket (OOP) costs between individuals receiving oncology biosimilars versus oncology reference branded products. Methods: This retrospective cohort study included adult commercial fully insured and Medicare members of a large national payor with ≥1 claim for a physician-administered oncology biosimilar or reference branded product between 12/01/2020 and 11/30/2022. To assess adherence, we compared claims per month, defined as the total claims during the study divided by the number of months patients received medication and time on therapy, defined as the number of months between first claim in period and last claim in period (inclusive). OOP costs, defined as the sum of deductible and applicable coinsurance at the time of visit, were examined as a secondary endpoint. Continuous variables were compared with Student’s t-test; categorical variables were compared with a Chi-squared test. P values < 0.05 were considered significant. Results: 2,597 individuals were included in the evaluation with between-group differences in age, gender, and agent received (all p < 0.001). 41,182 claims were evaluated; 59.2% were for reference branded products. 3,817 medication combinations were evaluated; 64.2% received a reference branded product. Individuals receiving biosimilar agents had more total claims (mean [standard deviation, SD]: 13.9 [6.3] vs. 13.1 [7.5]; p = 0.003) and claims per month (1.4 [0.5] vs. 1.3 [0.6]; p < 0.001). However, individuals receiving reference branded products had longer time on therapy (10.5 [4.1] vs. 10.0 [3.7] wk; p = 0.006). When examining oncology agents only (n = 1,992), individuals receiving biosimilar agents had more claims per month (1.4 [0.5] vs. 1.3 [0.6]; p < 0.001). In contrast, individuals receiving reference branded products had longer time on therapy (11.0 [4.1] vs. 10.1 [3.7] wk; p < 0.001). Individuals prescribed oncology support reference branded products and oncology treatment reference branded products experienced 475% and 350% higher OOP spend compared to individuals prescribed biosimilars (both p < 0.001), respectively. Conclusions: This real-world evaluation leveraging administrative claims revealed that individuals receiving oncology biosimilars appear to experience shorter observed time on therapy, higher adherence, and lower OOP spend than individuals receiving reference branded products. Despite superior member-centric outcomes, reference branded products were prescribed more often than biosimilars.