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Aim:Use of combination antibiotics piperacillin-tazobactam (PTZ) and vancomycin (VAN) is so often used as “top guns” for severe infections in hospitalized patients. VAN’s nephrotoxicity is well-known. PTZ has been seen to prolong increased creatinine levels. Reports have surfaced higher rates of acute kidney injury (AKI) among patients treated with combination of PTZ + VAN in the literature. The purpose of this study was to compare the prevalence of AKI with the use of VAN alone and combination of PTZ + VAN treatment at our institution. Our hypothesis was that the combination of PTZ + VAN would be associated with higher prevalence of AKI compared with VAN only.Materials and Methods:We performed this study to compare the combination of PTZ + VAN and VAN alone in critically ill patients in our hospital from 2016 to 2018. Included patients were stratified by treatment with PTZ + VAN and VAN alone.Results:A total of 113 patients were included who were treated with PTZ + VAN and VAN alone. Patient demographics, comorbidities, sites of infection, and duration for 48 hours were compared. We found that PTZ + VAN was better than VAN alone in terms of AKI.Conclusion:The combination of VAN plus PTZ is better use to prevent AKI over VAN monotherapy. Further research in the critically ill population is needed. Recent literature has suggested that the concomitant use of PTZ and VAN is associated with a higher risk of AKI compared with the use of VAN alone. Our study suggested that patients getting combination therapy were sicker hence receiving it as an empiric therapy and it is required to look at the possibility of residual confounding in previous studies.