Gebresillassie BM, et al. – This work was designed to determine the use of cotrimoxazole as a prophylaxis therapy among patients living with HIV/AIDS at Gondar University Referral Hospital (GURH), northwestern Ethiopia. Despite inconsistency with WHO guidelines regarding the practice of discontinuation of Cotrimoxazole preventive therapy (CPT) and follow–up for adverse drug effects on the rational use of cotrimoxazole prophylaxis, the use of CPT among people living with HIV/AIDS at GURH was appropriate. Authors recommend health professionals who were working in the antiretroviral therapy units to update themselves and adhere to the available updated guidelines to reduce the occurrence of adverse effects and prophylaxis failure.