Measuring the level of B-type natriuretic peptide (BNP), as a guide to pharmacotherapy, can increase the survival of patients with heart failure. This study is aimed at systematically reviewing the studies conducted on the cost-effectiveness of BNP-guided care in patients with heart failure. Using the systematic review method, we reviewed the published studies on the cost-effectiveness of BNP-guided care in patients with heart failure during the years 2004 to 2017. The results showed that all studies clearly stated the time horizon of the study and included direct medical costs in their analysis. In addition, most of the studies used the Markov model. The quality-adjusted life years (QALYs) were the main outcome used for measuring the effectiveness. The studies reported various ranges of the incremental cost-effectiveness ratio (ICER); accordingly, the highest ratio was observed in the USA ($32,748) and the lowest ratio was observed in Canada ($6251). Although the results of the studies were different in terms of a number of aspects, such as the viewpoint of the study, the study horizons, and the costs of expenditure items, they reached similar results. Based on the results of the present study, it seems that the use of BNP or N-terminal pro-BNP (NT-pro-BNP) in patients with heart failure may reduce cost compared to the symptom-based clinical care and increase QALY. In this regard, these studies were designed and conducted in high-income countries; thus, the application of these results in low- and middle-income countries will be limited.