Background: High prescription copayments may create barriers to care, resulting in medication nonadherence. Although many studies have examined these associations in commercially insured patients with chronic disease, few have examined beta-blocker effects in heart failure patients. Objective: Associations between beta-blocker prescription copayment levels and medication nonadherence were examined within commercially insured beneficiaries with a diagnosis of heart failure. Methods: Heart failure patients were identified as those with at least 1 inpatient claim or 2 outpatient claims with an associated International Classification of Diagnosis, 9th Edition (ICD-9) code of 428.x, in addition to those with at least 2 beta-blocker claims. Copayment levels were defined in using $5.00 (USD) interval categories, and adherence was defined using the medication possession ratio (MPR). Ordinary least squares (OLS), fixed effects (FE), and random effect (RE) models were used to estimate associations between copayment level and MPR. Logistic regression was used to estimate the probability of nonadherence (MPR < 0.80) conditional upon copayment level. Regressions controlled for patient demographics, health status, prior hospitalizations, and concomitant medication use. Results: The highest beta-blocker copayment level ($26+) had an average MPR that was 0.07 (95% CI, -0.11 to -0.03), 0.08 (95% CI, -0.12 to -0.04), and 0.09 (95% CI, -0.17 to -0.02) units lower than P-blocker copayment level ($0 to $1) in the OLS, RE, and FE models, respectively. Copayment levels $21-$25 and $26+ were significantly associated with an increased risk of medication nonadherence (OR = 1.64; 95% CI, 1.1-2.4; and OR = 2.5; 95%, CI 1.6-4, respectively). Conclusions: Commercially insured heart failure patients aged >= 50 years who are prescribed higher costing beta-blockers may have up to an average 9% decrease in annual beta-blocker medication supply as well as an increased risk of nonadherence (MPR <0.80). Results need to be interpreted with caution given the potential of selection bias due to selective prescribing. Associations between copayment levels and nonadherence need to be further explored given the adverse health consequences of nonadherence to beta-blockers. (Clin Ther. 2011;33:608-616) (C) 2011 Published by Elsevier HS Journals, Inc.