OBJECTIVES: Increasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for, and quantification of, these events is required for safe-use. This study aims to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting. METHOD: Patients prescribed cotrimoxazole were identified using electronic-healthcare records over three years (01/04/2016-31/03/2019). Individual risk-factors were recognised. Serum creatinine and potassium trends were analysed over the subsequent 21-days. AKI and hyperkalaemic patients were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed. RESULTS: Among 214 patients prescribed co-trimoxazole, 42 (19.6%, 95%CI 14.6-25.7%) met AKI criteria and 33 (15.4%, 95%CI 11.0-21.1%) developed hyperkalaemia. Low baseline eGFR (<60mls/min/1,73m2, OR=7.78, 95%CI 3.57-16.13, p<0.0001) and cardiac disorders (OR=2.40, 95%CI 1.17-4.82, p=0.011) predicted AKI, while low baseline eGFR (<60mls/min/1.73m2, OR=6.80, 95%CI 3.09-15.06, p<0.0001) and higher baseline serum potassium (p=0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920mg/day) was associated with lower AKI and hyperkalaemia risk (p=0.007 and 0.019, respectively). Early (within first 2-4 days of therapy) serum creatinine changes predicted AKI (OR=3.65, 95%CI 1.73-7.41, p=0.001), and early serum potassium changes predicted hyperkalaemia (>0.6mmol/l, OR=2.47, 95%CI 1.14-5.27, p=0.0236). CONCLUSIONS: Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose-dependent. Renal function, serum potassium and pre-existing cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2-4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose prescribed.