OBJECTIVES: With the rapid changes in oncology treatment and care, there is increasing concern regarding the financial burden of medications among cancer survivors. The objective of this study was to compare out-of-pocket (OOP) spending and medication affordability among Medicare beneficiaries with and without cancer. METHODS: A population-based retrospective cross-sectional study was conducted using the national representative sample of elderly beneficiaries from Medicare Current Beneficiary Survey. We compared annual OOP spending for prescription drugs and prevalence of Cost-Related Nonadherence (CRN; skipping or reducing doses, not obtaining prescriptions) and medication affordability (spending less on basic needs to afford medicines) among beneficiaries with and without cancer. Logistic regression models were performed to estimate the Odds Ratio (OR) of CRN and affordability. Adjusted OOP spending per beneficiaries was estimated using a generalized linear model. RESULTS: Compared with those not reporting cancer, cancer survivors were older with a higher prevalence of cigarette smoking, comorbidities, and prescription drug coverage. Among cancer survivors, 11.9% experienced CRN, compared with 9.2% of beneficiaries who haven’t been diagnosed with cancer (p=0.01), while there were no significant differences in the rate of spending less on basic needs between beneficiaries with and without cancer (3.9% vs. 3.4%; p=0.32).  Additionally, cancer survivors had significant higher annual OOP spending for prescription drugs than beneficiaries without cancer ($628.2 vs. 515.6; p=0.02). After adjusting for demo-socioeconomic and clinical characteristics, the adjusted OR of reporting CRN among cancer survivors was 1.33 (95% Confidence Interval [CI]=1.04-1.70), compared to those without cancer. However, there was no significant differences in the likelihood of spending less on basic needs between cancer survivors and those with cancer (OR= 1.152; 95% CI=0.87-1.52). CONCLUSIONS: The findings indicated that cancer survivors had substantially higher out-of-pocket spending and prevalence of Cost-Related Nonadherence. More efforts should be focus on improving economic access to prescriptions among cancer survivors.