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Background: Visual impairment can severely affect the quality of life, with a tremendous negative impact on job performance and socioeconomic status. This substantially affects the psychological status of people with visual impairment. Objective: This study aimed to determine the prevalence and factors associated with psychological distress among visually impaired Ethiopian adults attending the University of Gondar Tertiary Eye Care and Training Center. Methods: A comparative cross-sectional study was conducted at the University of Gondar Tertiary Eye Care and Training Center in Gondar City, northwest Ethiopia. A total of 206 adults with visual impairment (a presenting VA ≤ 6/18 in at least one eye) and 206 adults with normal vision were included in the study. Psychological distress was measured using a standardized self-reporting questionnaire (SRQ-20). Chi-square and binary logistic regression analysis were performed. Variables with a P-value of less than 0.05 were considered statistically significant. Results: The overall prevalence of psychological distress in the study participants was 31.07% (95% CI: 26.2, 35.8). Psychological distress was higher (43.2%; 95% CI: 36.5, 50.5) and statistically differed (p = 0.02) in visually impaired compared to adults with normal vision (18.9%; 95% CI: 14.1, 24.3). Duration of vision loss ≥ 2 years (AOR = 8.70; 95% CI: 2.38, 31.46), sudden loss of vision (AOR = 3.50; 95% CI: 1.10, 18.30), unmarried (AOR = 5.53; 95% CI: 1.66, 18.43), living lonely (AOR = 8.40; 95% CI:1.48, 4.74), College and above educational status (AOR = 2.50; 95% CI:1.47, 10.61), and loss of vision in both eyes (AOR = 1.70; 95% CI: 2.00, 14.10) were variables with a significant association with psychological distress among visually impaired adults. Conclusion: This study revealed that the prevalence of psychological distress was significantly higher among visually impaired adults than among adults with normal vision. The effect of visual impairment on psychological distress was significantly related to marital status, living arrangements, educational status, duration of vision loss, pattern of vision loss, and laterality of vision loss. [ABSTRACT FROM AUTHOR]