OBJECTIVES: To identify published cost-effectiveness analyses and health technology assessment (HTA) submissions for treatments in chronic heart failure (CHF) to inform future cost-effectiveness modeling in CHF. METHODS: A systematic review was performed. Literature searches were conducted in MEDLINE, EMBASE, EconLit, and the Cochrane Library, with supplementary hand searching of conferences and HTA websites. Eligible studies had to report on cost-effectiveness outcomes in adults with CHF and/or heart failure with reduced ejection fraction, treated with angiotensin-converting enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor blockers, or ivabradine. RESULTS: Sixty-six publications met the inclusion criteria, representing 63 distinct analyses. Of these, 53 reported their methods: 20 were statistical analyses of individual patient data, while 33 used decision-analytic modeling. Structures were most commonly described as being Markov (n=27) but the methods were heterogeneous. The health states most frequently employed were ‘alive’ or ‘dead’, with outcomes such as hospitalization or New York Heart Association (NYHA) class distribution most commonly considered as a partition of the ‘alive’ state. Other health states considered were often based on NYHA class, hospitalizations, and major CV events. Different approaches to modeling the effects of interventions on mortality were used; treatment effects were applied to cardiovascular (CV) mortality and all-cause mortality in nine and 20 studies (among the 33 decision-analytic models), respectively. Across included studies, the time horizon ranged from within-trial to lifetime. Outcomes were frequently sensitive to baseline risks of mortality and hospitalization, relative efficacy of interventions, and unit costs of interventions. CONCLUSIONS: The studies identified were heterogeneous with respect to their approaches; this may be due to the preference of payers in different jurisdictions. However, the identified literature suggests mortality and hospitalization are the key determinants of the cost-effectiveness of treatment for CHF.