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Introduction: Acquired immune deficiency syndrome is a disease with common clinical ocular manifestations. Ocular manifestations lead to blindness, which has a common social and economic impact., Purpose: This study aimed to assess the prevalence and associated factors of ocular manifestations of acquired immune deficiency syndrome among adults at the University of Gondar Hospital, North West Ethiopia, 2021., Patients and Methods: A cross-sectional study was conducted on 401 patients from June to August 2021. Samples were selected based on a systematic random sampling technique. Data collection was done using structured questionnaires. Data extraction format was used to collect the clinical characteristics of patients including ocular manifestations. Data entry was done by EpiData version 4.6.0.6 and exported to the Statistical Package for the Social Sciences version 26 for data analysis. Associated factors were analyzed by binary logistic regression. P-value <0.05 with a 95% confidence level was used to declare a significant association., Results: A total of 401 patients were involved with a response rate of 91.5%. The overall prevalence of ocular manifestations of acquired immune deficiency syndrome was 28.9%. The common ocular manifestations were seborrheic blepharitis at 16.4% and squamoid conjunctival growth at 4.5%. Age >35 years (AOR=2.52, 95% CI: 1.19, 5.35), Clusters of differentiation 4 count <200 cells/µL (AOR=4.76, 95% CI:2.50, 9.09), World Health Organization stage II (AOR=2.60, 95% CI: 1.23, 5.50), history of eye disease (AOR=3.05, 95% CI: 1.38, 6.72), and duration of Human Immunodeficiency Virus >5 years (AOR=2.79, 95% CI: 1.29, 6.05) were statistically associated with the ocular manifestation of acquired immune deficiency syndrome., Conclusion and Recommendations: In this study, the prevalence of ocular manifestation of acquired immune deficiency syndrome was high. Age, CD4 count, duration of HIV, eye disease history, and WHO clinical staging were the significant factors. Early eye checkups and regular ocular examinations of HIV patients would be helpful., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Aragaw et al.)