Antibiotics induced acute kidney injury (AKI) risk in critically ill patients is not well known. This study aimed to evaluate the AKI development and clinical outcomes in critically ill adult patients treated with vancomycin (VAN) or combined with piperacillin-tazobactam (TZP) or meropenem (MEM). This was a retrospective study on critically ill adult patients who were given VAN, TZP or MEM and maintained for at least 48 h. The risk of AKI development and clinical outcomes were compared using the simple analysis and multivariate logistic regression. Three hundred forty patients were eligible. The incidence of any AKI was significantly higher in patients treated with VAN + TZP than those with VAN + MEM or VAN alone (52.7% vs. 27.7% vs. 25.7%; p < .0001). The adjusted odds of AKI increased 2.43-fold in VAN + TZP versus VAN, but not different in VAN + MEM versus VAN. However, AKI duration and recovery rate were not statistically different. In addition, all-cause death within 30 days after AKI onset was not significantly associated with antibiotic regimens. AKI incidence is higher in critically ill patients administered with VAN + TZP than those with VAN + MEM or VAN. However, no obvious evidence was found to prove that antibiotic-induced AKI leads to poor clinical outcomes.