Objective: The purpose of the study was to investigate the relationship between prescription copay and adherence with renin-angiotensin system (RAS) therapy in heart failure patients. Methods: Data for this study came from a large national pharmacy benefit manager's clients. A retrospective data analysis was used to identify patients who had a diagnosis of heart failure (ICD-9 code 428) between July 1, 2003 and June 30, 2006. The discharge date of the first hospitalization after the 6-month baseline was designated as the index date. Patients' pharmacy claims were followed for one year after their index dates. Adherence with RAS therapy was measured by medication possession ratio (MPR). Prescription copay was measured by a flat dollar amount paid for RAS therapy, normalized at days of supply level. Regression analyses were adopted to analyze the effects of copay on adherence with RAS therapy. Other control variables included age, gender, comorbidities, concomitant medications (b-blockers, statins, calcium channel blockers), and the step-therapy care program. Results: The results show that of the 799 heart failure patients, 457 (57%) received RAS therapy. 48% of the 457 patients were adherent (MPR = 0.8), 22% were partially adherent (0.5 = MPR <0.8) and 30% were non-adherent (MPR <0.5). Prescription copay had a significant negative effect on adherence, which meant higher copayment led to lower adherence rates such that for every $1 increase in prescription copay, adherence decreased by 9%. Of the controlling variables, only age had a positive impact on adherence where older individuals were more compliant with RAS therapy than younger people. Conclusion: Approximately 4 out of 10 patients did not receive recommended pharmacotherapy with RAS agents after a heart failure event. Furthermore, only half of those patients who received RAS therapy were considered adherent. Higher prescription copay was associated with lower adherence to RAS therapy.