Abstract Background: Co-trimoxazole is a broad-spectrum antibiotic associated with hyperkalemia, particularly in those with additional risk factors. Objectives: To determine the incidence of hyperkalemia and its risk factors in patients receiving co-trimoxazole. Methods: A retrospective observational study involving all patients who received co-trimoxazole between 1 January 2012 and 1 January 2013. Subjects were identified through a list generated from a computerized pharmacy system. The patients’ demographic and clinical characteristics were retrieved from electronic medical records. Data were analyzed using univariate and multivariate logistic regression. Results: One hundred sixty-one patients fulfilled the eligibility criteria. Of these, 46 (28.6%) experienced hyperkalemia. Around 35 (76.1%) of the patients who experienced hyperkalemia received co-administered medications that might induce hyperkalemia. The co-administration of co-trimoxazole with other medications that may induce hyperkalemia was found to be associated with higher incidence of hyperkalemia when compared to co-trimoxazole administration alone [adjusted OR 3.2, 95% CI (1.4-7.3), p=0.005]. Additionally, age > 60 years was associated with an increased risk of hyperkalemia when compared to younger age group 18-39 years [adjusted OR 6.5, 95% CI (2.1-19.7); p=0.001]. Conclusion: Caution should be exercised in older patients and those receiving co-trimoxazole in combination with other medications, such as immunosuppressants and β-blockers that might contribute to hyperkalemia development. Keywords: Co-trimoxazole, co-administration, hyperkalemia, risk factors, adverse drug reaction