Human Immunodeficiency Virus (HIV) is among the highest health crises that humanity ever confronted and it causes progressive weakening of the immune system leading to opportunistic infections (OIs) or malignancies during the natural course of the disease. This study aimed at assessing the prevalence and factors associated with the occurrence of OIs among adult PLWHIV on antiretroviral therapy (ART) at Ruhengeri referral hospital. Methodology A cross-sectional study was performed by reviewing

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... cords of HIV-positive adult (≥ 15 years) on ART enrolled at Ruhengeri referral hospital from 1st January 2007 to 31st December 2017. Opportunistic infections were reported based on clinical diagnosis and the prevalence of OIs was determined. Results The study reviewed records from 423 PLWHIV. Thirty-nine (9.2%) PLWHIV had been diagnosed with OIs; and frequent OIs were tuberculosis (20%), oral candidiasis, pneumonia and STI (15.6% each). The independent risk factors for developing OIs were being jobless (AOR = 5.03, 95% CI = 2.13, 32.99), spending more than five years on ART (AOR = 4.34, 95% CI = 1.12-16.78) and starting ART at WHO clinical stage III (AOR = 4.88, 95% CI = 1.65-16.78). Conclusion There is a need to strengthen the management of opportunistic infections despite the use of ART at Ruhengeri referral hospital. Rwanda J Med Health Sci 2022;5(3):323-331