Objective To evaluate the clinical effect and safety of western medicine plus Shenmai Injection versus western medicine alone for heart failure (HF) patients. Methods We searched CNKI (January 1979 to April 2009), VIP (January 1989 to April 2009), CBM (1978 to 2009), PubMed (1978 to April 2009), The Cochrane Library (Issue 3, 2009), and other relevant databases and journals to identify randomized controlled trials (RCTs) about western medicine plus Shenmai Injection versus western medicine alone for HF patients. The methodological quality was assessed and the data was extralted according to the Cochrane Reviewer’s Handbook and related methods. Meta-analyses were performed using RevMan 5.0.2 software.Results Fifteen eligible studies involving 1174 HF patients were included. The results of meta-analyses showed that western medicine plus Shenmai Injection therapy could precisely improve the general therapeutic effects (RR=1.27, 95%CI 1.19 to 1.35, Plt;0.000 01), increase left ventricular ejection fraction (WMD=7.17, 95%CI 4.65 to 9.70, Plt;0.000 01), and make ventricular diastolic function better (minor weight literature: WMD=0.38, 95%CI 0.32 to 0.45, Plt;0.000 01; major weight literature: WMD=0.38, 95%CI 0.32 to 0.45). Meanwhile, only one study indicated that western medicine plus Shenmai Injection could increase 6-minute walking distance, reduce BNP, IL-6, and TNF-α levels, respectively. Conclusion By comparison with western medicine alone, western medicine plus Shenmai Injection can improve the therapeutic effect on HF patients.