Background: Little is known about the specific out-of-pocket costs which may lead to prescription nonadherence in older cancer survivors, and how patterns may differ for those living in rural areas. This study quantified patient costs overall and by residence for older cancer survivors who did and did not report cost-related prescription nonadherence. Methods: This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results Program, Medicare claims, and the Consumer Assessment of Healthcare Providers and Systems survey linked data resource (SEER-CAHPS) from 2007-2015. Older cancer survivors self-reported cost-related prescription nonadherence in the prior six months. Patient cost responsibility (deductibles, coinsurance, copayments) was summed for all medical care received in the year prior to survey. Differences in patient cost responsibility by cost-related adherence was estimated using gamma generalized linear models adjusted for patient age, race, sex, education, dual Medicaid enrollment status, residence, comorbidity count, cancer type, stage, and phase of care. Models stratified by urban/rural residence as designated by Rural-Urban continuum codes assessed effect modification. Results: Of 11,829 older adult survivors of prostate (37%), breast (32%), colorectal (14%), gynecologic (10%), or lung (6%) cancer, 12% reported any cost-related prescription nonadherence in the prior year. Median age of survivors was 76 (interquartile range [IQR] 71-82), 15% had less than a high school degree, 59% had at least one non-cancer comorbidity, and 16% had ever been dual eligible. Prevalence of cost-related nonadherence was similar by patient characteristics. Median cost responsibility in the year prior to survey was $1,529 (IQR $744-$2,959) for patients reporting nonadherence and $1,123 (IQR $572-$2,362) for those reporting adherence. In adjusted models, patients reporting nonadherence had $656 higher patient cost responsibility in the year prior (95% CI $564-$760) compared to those reporting adherence. Approximately half of the difference in cost was outpatient spending (β = $277, 95% CI $210-$359). Differences in cost responsibility for patients reporting nonadherence compared to adherence were smaller for patients residing in rural areas (18% of respondents; β = $341, 95% CI $177-$564) compared to those residing in urban areas (82% of respondents; β = $715, 95% CI $613-$830). Conclusions: Compared to those reporting adherence, cost-related prescription nonadherence was associated with higher health care cost responsibility in cancer survivors. Furthermore, prescription adherence decisions may be more cost-sensitive for patients living in rural compared to urban areas. Interventions to address out-of-pocket health care costs, particularly for rural cancer survivors, could aid in increased prescription adherence and subsequent health outcomes.