The role of B-type natriuretic peptide (BNP) in the management of patients with chronic heart failure (CHF) was uncertain. The aim of this meta-analysis was to comprehensively evaluate the effect of BNP-guided therapy in CHF. Relevant randomized controlled trials were identified by searching of Pubmed, Embase and the Cochrane Library databases. Fixed or randomized effect models were applied to combine the data according to the heterogeneity of the included studies. Fourteen studies with 3,004 CHF patients were included. Results of our meta-analyses suggested that compared with clinical group, BNP-guided treatment significantly decreased the risk of heart failure-related hospitalization (RR 0.79, 95 % CI 0.63–0.98, p = 0.03), although did not significantly affect the risk of all-cause mortality (RR 0.94, 95 % CI 0.81–1.08, p = 0.39) or all-cause hospitalization (RR 0.97, 95 % CI 0.89–1.07, p = 0.56). Furthermore, between-group BNP changes seemed to be a significant modifier to the effects of BNP-guided therapy on clinical outcomes, and BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. In addition, BNP-guided therapy was not associated with increased risk for serious adverse events. BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. BNP-guided therapy seemed to be safe and promising for CHF patients, and future studies with well-designed BNP-guided medication up-titration strategies are needed to confirm these results.