Abstract: Objective To investigate the effect of tolvaptan combined with levosimendan on cardiac function and heart rate variability(HRV)in elderly patients with refractory heart failure(RHF). Methods A total of 125 elderly patients with RHF were randomly divided into observation group(63 cases)and control group(62 cases). On the basis of conventional treatment, the control group was treated with tolvaptan, and the observation group was treated with levosimendan on the basis of the control group. Cardiac function ［left ventricular ejection fraction(LVEF), stroke volume(SV), N-terminal B-type natriuretic peptide(NT-proBNP)］, HRV ［standard deviation of 24 h normal RR interval(SDNN), standard deviation of average RR interval(SDANN), root mean square difference of adjacent RR intervals(RMSSD)］ and oxidative stress indicators ［malondialdehyde(MDA), total antioxidant(TAS), lipid peroxide(LPO)］ were compared between the two groups. Results After 7 days of treatment, the cardiac function indexes of the observation group were significantly better than those in the control group(P<0.05); the HRV indexes in the observation group were significantly higher than those in the control group(P<0.05). TAS in the observation group was significantly higher than that in the control group(P<0.05), MDA and LPO were significantly lower than those in the control group(P<0.05). Conclusion Tolvaptan combined with levosimendan can reduce the degree of oxidative stress and myocardial injury, and improve cardiac function and HRV in elderly patients with RHF.