• Piperacillin/tazobactam (PT) is widely used in adults worldwide, and is recommended in various guidelines. • Increased risk of acute kidney injury (AKI) in those who used PT and vancomycin concomitantly raises concern about the safety of PT administration. • In this real-world data analysis of hospitalized adults in China, PT without concomitant use of vancomycin was not associated with increased risk of hospital-acquired AKI compared with other antipseudomonal beta-lactams (meropenem or ceftazidime). • In adults hospitalized with infection, concern regarding the risk of AKI may not be an important consideration in the choice of PT compared with meropenem or ceftazidime if not used in combination with vancomycin. There is uncertainty about whether piperacillin/tazobactam (PT) increases the risk of acute kidney injury (AKI) in patients without concomitant use of vancomycin. This study compared the risk of hospital-acquired AKI (HA-AKI) among adults treated with PT or antipseudomonal β-lactams (meropenem, ceftazidime) without concomitant use of vancomycin. This real-world study analysed the data from China Renal Data System and assessed the risk of HA-AKI in adults hospitalized with infection after exposure to PT, meropenem or ceftazidime in the absence of concomitant vancomycin. The primary outcome was any stage of HA-AKI according to the Kidney Disease Improving Global Outcomes guidelines. A multi-variable Cox regression model and different propensity score (PS) matching models were used. Among the 29,441 adults [mean (standard deviation) age 62.44 (16.84) years; 17,980 females (61.1%)] included in this study, 14,721 (50%) used PT, 9081 (31%) used meropenem and 5639 (19%) used ceftazidime. During a median follow-up period of 8 days, 2601 (8.8%) develped HA-AKI. The use of PT was not associated with significantly higher risk of HA-AKI compared with meropenem [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.97–1.19], ceftazidime (aHR 1.09, 95% CI 0.92–1.30) or both agents (aHR 1.07, 95% CI 0.97–1.17) after adjusting for confounders. Results were consistent in stratified analyses, PS matching using logistic regression or random forest methods to generate a PS, and in an analysis restricting outcomes to AKI stage 2–3. Without concomitant use of vancomycin, the risk of AKI following PT therapy is comparable with that of meropenem or ceftazidime among adults hospitalized with infection. [ABSTRACT FROM AUTHOR]