Objective To observe tolvaptan combined with diuretic treating heart failure with water retention patients in influencing serum sodium levels and the prognosis. Methods 92 cases of heart failure with water retention patients admitted and treated in our hospital during March 2014 and June 2015 were selected as the study objectives. They were randomly divided into contrast group and observation group with 46 cases in each group. Patients in the contrast group were given conventional anti-heart-failure treatment like diuretic, while patients in the observation group were given treatment of tolvaptan combined with diuretic. Observe the serum sodium levels changing of before and after treatment. Compare the clinical curative effects as well as the cardiovascular event occurrence condition between both groups. Results Before treatment, the comparison of serum sodium levels between both groups showed no statistical significance (P>0.05). After treatment, the serum sodium levels in the observation group were significantly higher than the contrast group. The difference showed a statistical significance (P<0.05). The total effective rate in the observation group (91.30%) was significantly higher than the contrast group. And the occurrence rate of cardiovascular event was obviously lower than the contrast group. The difference showed a statistical significance (P<0.05). Conclusion Tolvaptan combined with diuretic is proved to be effective in treating heart failure with water retention patients, which helps to increase the serum sodium levels and redress the electrolyte balance with significant curative effects. Thus, it deserves to be widely promoted in clinical field.