OBJECTIVE: To evaluate clinical effect and safety of tolvalptan in the treatment of diuretic-resistant heart failure. METHODS: The clinical data of 21 inpatients with diuretic-resistant heart failure in cardiology department of the First Affiliated Hospital of Chongqing Medical University during Jan. 2014-Aug. 2016 were analyzed retrospectively. The heart failure improvement of 21 patients was not obvious after the treatment of a large dose of loop diuretics (furosemide and/or torasemide), and then the treatment was changed into tovalptan. Among them, 19 patients were treated with Tovalptan tablets 7.5 mg orally, qd, and 2 patients were treated with Tovalptan tablets 15 mg orally, qd, continuously until the patients discharged. The cardiac function, edema, outcome and body weight, blood pressure, blood sodium, blood creatinine and blood NT-proBNP levels, the change of urine volume per unit time were compared among 21 patients before and after treatment. The occurrence of ADR was observed. RESULTS: After treatment, cardiac function of 21 patients were improved significantly, edema and systolic blood pressure were decreased significantly while blood sodium and urine volume per unit time were increased significantly, with statistical significance (P<0.05). There was no statistical significance in body weight, diastolic blood pressure, blood creatinine or blood NT-proBNP levels before and after treatment (P>0.05). Among 21 patients, one patient suffered from dry mouth; systolic blood pressure of 3 patients decreased by 20 mmHg or above, compared to basic value; diastolic blood pressure of 4 patients decreased by 10 mmHg or above, compared to basic value. CONCLUSIONS: For diuretic-resistant patients, tolvaptan can increase urine volume, improve cardiac function and correct hyponatremia, besides it also lowers the systolic blood pressure.