Background: Tolvaptan is a promising drug for the prevention of contrast-induced acute kidney injury (CI-AKI) because it induces aquaresis without adversely affecting renal hemodynamics. CI-AKI is a major cause of acute renal failure associated with increased morbidity and mortality. Objective: To investigate the effectiveness of different doses of tolvaptan for the prevention of CI-AKI. Method: Ninety-one consecutive patients with congestive heart failure (CHF) and chronic kidney disease (CKD) were prospectively enrolled as the tolvaptan group in this study (T-group; 7.5-mg: n = 42, 15-mg: n = 49). In addition, 91 consecutive patients with CHF and CKD were collected retrospectively as a control group (C-group, n = 91). All patients received continuous intravenous infusion of isotonic saline, and tolvaptan was administered to the T-group. Results: One patient developed CI-AKI in the T-group versus 3 in the C-group (1.1 vs. 3.3%, p = 0.61). On the other hand, the change of serum creatinine in the T-group was lower than that in the C-group. Additionally, in the 7.5-mg group, serum creatinine was unchanged up to 72 h after contrast administration, showing a significant difference from the 15-mg group (-0.00 ± 0.09 vs. 0.05 ± 0.12 mg/dL, p = 0.009). Similarly, the change of eGFR was significantly smaller in the 7.5-mg group than that in the 15-mg group (0.7 ± 5.4 vs. -2.8 ± 5.1 mL/min/1.73 m2, p = 0.002). No patient required hemodialysis and there was no prolongation of hospitalization due to exacerbation of heart failure. Conclusions: Compared to hydration alone, tolvaptan combined with hydration could be a safer method for preventing CI-AKI while avoiding exacerbation of heart failure, and a dosage of 7.5-mg might be safer than 15-mg.