Background Renal dysfunction is a common comorbidity in acute heart failure (AHF) patients. The prognostic significance of early treatment with tolvaptan in AHF patients complicated with renal dysfunction has not been elucidated. Methods Post hoc analysis was performed on a randomized clinical study for prespecified prognostic endpoints and prespecified subgroups. 217 AHF patients with renal dysfunction (eGFR 15 to 60mL/min/1.73m 2 ) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. Results During follow-up (636days, median) 99 patients experienced combined endpoint and 53 patients died. There was no significant difference in event-free survival rate for either the combined events (Log-rank: P=0.197) or all-cause death (Log-rank: P=0.894) between tolvaptan and conventional groups. In prespecified subgroup analysis, in patients whose BUN/creatinine ratio was above the median (>20), tolvaptan significantly reduced the risk of combined events (HR: 0.52, 95% CI: 0.30–0.91, P=0.021) with a significant interaction (P value for interaction=0.045). Likewise, in patients whose eGFR was 30mL/min/1.73m 2 or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32–0.90, P=0.017) with a significant interaction (P value for interaction=0.015). Conclusion Short-term use of tolvaptan in acute-phase in AHF with renal dysfunction showed a neutral effect on prognosis. Patients with relatively preserved renal function and relatively high BUN/creatinine ratios are potentially favorable subgroups for treatment with tolvaptan.