Background & Aims Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial. Methods A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1 g/kg on day 3; albumin group ALB: n = 96) or antibiotics alone (control group CG: n = 97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate. Results Forty-seven (24.6%) patients died (ALB: n = 27 vs. CG: n = 20; 3-month survival: 70.2% vs. 78.3%; p = 0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p = 0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p = 0.88). By multivariate analysis, MELD score ( p <0.0001), pneumonia ( p = 0.0041), hyponatremia ( p = 0.031) and occurrence of renal failure ( p <0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion. Conclusions In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.