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Kirubel Dagnaw Tegegne,1 Nigus Cherie,2 Fentaw Tadesse,2 Lehulu Tilahun,3 Mesfine Wudu Kassaw,4 Gebeyaw Biset5 1Department of Comprehensive nursing, College of medicine and Health Science, Wollo University, Dessie, Ethiopia; 2School of Public health, college of Medicine and Health science, Wollo University, Dessie, Ethiopia; 3Department of Emergency Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia; 4School of nursing, college of health science, Woldia University, Woldia, Ethiopia; 5Department of Pediatric Nursing, College of medicine and Health Science, Wollo University, Dessie, EthiopiaCorrespondence: Kirubel Dagnaw Tegegne, Tel +251938405728, Email kirubeldagnaw@gmail.comBackground: Opportunistic infections are the major causes for morbidity and mortality due to HIV infections. Despite advances in HIV diagnosis and management, the incidence of opportunistic infections remains high. This study aimed to assess the incidence and predictors of opportunistic infections among persons living with HIV/AIDS in Ethiopia.Methods: A retrospective follow-up study was conducted on 354 samples of adults living with HIV on antiretroviral therapy at Dessie Comprehensive Specialized Hospital. Simple random sampling technique was used to select study participants. The data collection format was taken from national antiretroviral intake and follow-up forms. Epi-data Version 4.6.1 and STATA Version 16 software were used for data entry and data analysis respectively. The Cox-proportional hazards regression model was fitted. Kaplan–Meier survival curve was used to estimate opportunistic infections-free survival time. Both bi-variable and multivariable Cox-proportional hazard regression analysis were done to identify predictors of opportunistic infections.Results: Of the total 354 peoples living with HIV, 114 (32.2%) developed OI, with an incidence rate of 13.5 per 100 person-year (95% CI: 10.8– 15.6). Advanced World Health Organization clinical disease stage (IV) (AHR: 2.1 (95% CI: 1.16, 3.8)), being bedridden (AHR: 1.66 (95% CI: 1.04, 2.65)), poor adherence (AHR: 1.7 (95% CI: 1.1– 2.63), and low CD4 count (AHR: 1.92 95% CI: 1.14– 3.22) were significant predictors of OIs.Conclusion: Opportunistic infection among HIV/AIDS continues to be a significant public health concern in Ethiopian health care setting. Our results indicate that the incidence of OI is high. Besides, Stage IV HIV status, being bedridden, low CD4 count and poor adherence independently predicts an increased incidence/decreased survival time of OIs among PLWHIV. Early care-seeking and initiation of HAART and continuous follow-up of patients to take their drug timely are essential to curb the incidence of opportunistic infections and improve overall health. Further research on this area is highly recommended.Keywords: incidence, predictors, opportunistic infections, HIV/AIDS, Dessie