Objective:The purpose of this study was to assess the efficacy and safety of Chinese herbal medicine (CHM) in the treatment of chronic heart failure (CHF) patients according to syndrome differentiation.Methods:In this multicenter,randomized,double-blind,placebo-controlled clinical trial,a total of 220 CHF patients were assigned to receive CHM or placebo granules without decoction according to syndrome differentiation in addition to their standard west treatment for 4 weeks.The change in the left ventricular ejection fraction (LVEF) was the primary outcome,and the changes in the TCM syndrome scores (TCM-SS) and New York Heart Association functional classification (NYHA-FC) were the secondary outcomes.Results:After 4 weeks of treatment,the mean changes in the LVEF (13.1 ± 9.78 vs.7.34 ± 7.40,P ＜ 0.001) and the TCM syndrome scores (-34.2 ± 24.6 vs.-23.5 ± 25.2,P =0.002) were better in the CHM group than in the placebo group.After two weeks of treatment,the mean changes in the LVEF (9.26 ± 7.83 vs.4.72 ± 5.60,P ＜ 0.001) and the TCM syndrome scores (-23.5 ± 18.6 vs.-14.0 ± 15.9,P ＜ 0.001) were better in the CHM group than in the placebo group.In addition,repeated-measures analysis of variance (ANOVA) indicated significant time course effects of CHM versus placebo in the LVEF and TCM syndrome cores (P ＜ 0.001 for aU).The distention of the jugular vein (P =0.021),expectoration (P =0.044),abdominal distention (P =0.004),and rib pain (P =0.005) were significantly less in the CHM group than in the placebo group after two weeks of treatment.Fatigue (P =0.001),less gas and lazy words (P =0.001),dizziness (P =0.003),gasping for breath (P =0.027),abdominal distention (P =0.011),nausea (P =0.001) and emesis (P =0.012) were significantly less in the CHM group than in the placebo group after treatment for four weeks.After four weeks of treatment,the change in the NYHA functional classification in the CHM group was better than that in the placebo group (P ＜ 0.001).There was one death in the placebo group,and one patient in the CHM group experienced atrial fibrillation.Conclusion:CHM treatment according to syndrome differentiation effectively improved the LVEF,TCM-SS,and NYHA-FC in patients with CHF and also appeared to be safe.Thus,CHM treatment could be used as an adjuvant therapy in the treatment of CHF (Clinical trial registration:NCT01939236).