Aim: To evaluate the risk of acute kidney injury (AKI) in patients who receive vancomycin (VNC) and piperacillin-tazobactam (PTZ) combination therapy. Method: A single centre, retrospective audit of adult patients treated with VNC alone and in combination with PTZ between 2014-2015. Data was extracted from digital medical records and therapeutic drug monitoring sheets completed by clinical pharmacists. Rates of AKI and duration of combination therapy were analysed by chi-square, with logistic regression analysis completed to control for nephrotoxins, intensive care unit admission, use of inotropes and pre-existing chronic kidney disease. Results: Out of 525 vancomycin courses, that met the inclusion criteria, 211 had PTZ co-prescribed during the study period. Combination therapy was significantly both associated with an increased rate of AKI compared to VNC use alone (17.5% vs 10.5%, P = 0.02). The mean duration of combination therapy was 4 days (1-17 days). Increased duration of exposure to combination therapy was also associated with a higher incidence of AKI (3.8 days vs. 5.2 days, P = 0.014). VNC-TPZ combination was identified to be an independent risk factor for AKI (OR 1.73, 95% CI 1.01-2.96, P = 0.046) after adjusting for other known risk factors for AKI, including vasopressor use and intensive care unit admission. Conclusion: Combined use of VNC-PTZ, as well as the duration of combination therapy are both associated with an increased risk of AKI compared with VNC alone. The results are similar to previous literature reports of AKI from the combination of antibiotics. Healthcare providers need to be vigilant and limit the exposure to this combination as clinically appropriate.