BACKGROUND: Urinary biomarkers may predict acute kidney injury (AKI) in cirrhosis with ascites in a moderate volume paracentesis setting. OBJECTIVE: The study aimed to assess the risk and consequence of AKI and its progression in patients with decompensated cirrhosis undergoing paracentesis using a urine test measuring tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7). METHODS: A randomized, controlled trial was performed. All outpatients with decompensated cirrhosis with ascites and diuretic complications were enrolled and randomized into 3 and 5 L paracentesis groups. Serial urine samples were analyzed for TIMP2. IGFBP7 concentration before and after paracentesis. RESULTS: A total of 90 patients with decompensated cirrhosis were consecutively enrolled during the study period. After screening, 29 patients were enrolled in the 3-L paracentesis group, and 25 patients were enrolled in the 5-L paracentesis group. The mean of the MELD score was 8 ± 1.2. Urine TIMP2.IGFBP7 > 2, rising urine TIMP2, and rising urine TIMP2/urine Cr were shown in patients within the 5-L group for 48% ( = 0.015), 32% ( = 0.049), and 76% ( = 0.010) respectively, indicating a higher incidence of renal tubular injury markers in this group. Urine TIMP2.IGFBP7/1000 > 2 was statistically significant to predict a hemodynamic event ( = 0.002). CONCLUSION: In cirrhotic patients with ascites undergoing paracentesis, a 5-L paracentesis volume was associated with a higher incidence of renal tubular injury markers. The national clinical registration number was TCTR20191116003.