Objectives: To investigate the safety and efficacy of Yangxinkang Tablets in patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency, blood stasis, and water retention. Methods: In a double-blinded, randomized, placebo-controlled, multicenter clinical trail, 228 patients with CHF New York Heart Association (NYHA) class II or III in stage C were assigned by randomized block method to two groups in a 1:1 ratio to undergo either conventional Western treatment or conventional treatment plus Yangxinkang Tablets for 4 weeks. The outcome measure were effect of cardiac function, Chinese medicine (CM) syndromes, scores of symptoms, signs, and quality of life measured by Minnesota Living with heart failure questionnaire (MLHFQ) before and after the treatment. Results: Totally 112 patients were analyzed in the treatment group and 109 in the control group. They were comparable in NYHA functional class, basic parameters and primary diseases before treatment. Cardiac function and CM syndromes were greatly ameliorated in both groups after treatment. Total effective rates of cardiac function and CM syndrome in the treatment group were significantly higher than those in the control group (P < 0.05). Total symptom score and sign score in the treatment group decreased significantly after treatment (P < 0.01), which were significantly lower than those in the control group (P < 0.05). There were statistically significant differences in post-treatment scores of gasp, cough with phlegm, pulmonary rales and jugular vein engorgement between the two groups (P < 0.05 or P < 0.01). Three MLHFQ scores decreased significantly in both groups after treatment (P < 0.01). Post-treatment total scale score and physical subscale score in the treatment group and the reduction of them showed statistically significant differences (P < 0.05) as compared with the control group. There was no significant difference between the two groups in emotional subscale score and the reduction after treatment (P > 0.05). There was no obvious adverse reaction in either group noted during the study. Conclusions: Yangxinkang Tablets were safe and efficacious in improving cardiac function, CM syndromes, symptoms, signs, and quality of life in patients with CHF class II or III in stage C on the base of conventional treatment.