PURPOSE: To investigate the representation of various gender, racial, and ethnic groups in ophthalmology clinical trials conducted in the United States (US) between 1997 and 2022. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: We included all participants in completed phase II/III, III, and IV ophthalmology clinical trials reported on the ClincialTrials.gov database. METHODS: The proportional enrollment of each racial/ethnic and gender group in the clinical trials was calculated and compared with the US population. We also investigated the impact of various clinical trial features on the rate of reporting demographic information and enrollment of minorities. MAIN OUTCOME MEASURES: Proportional enrollment of each gender and race/ethnicity group compared with the US Census. RESULTS: Of the total clinical trials included in the study, less than half (43.6%) provided information on the racial or ethnic backgrounds of their participants. The majority of the enrollees in trials were female (median: 57.5%, interquartile range [IQR]: 47.2%-65.8%). Among the trials that reported race and/or ethnicity data, White populations were overrepresented (median: 76.6%, IQR: 69.0%-84.0%, P = 0.001), and minorities, including Asian, Hispanic, and other groups, were underrepresented compared with the 2010 US Census (P < 0.001). Enrollment of Black individuals was found to be comparable to the US population estimates (median: 12.4%, IQR: 6.2%-20.8%, P = 0.44). The trial phase, the number of study participants, the primary clinical condition, and the year the trial started all affected demographic reporting and minority enrollments. CONCLUSIONS: Our findings highlight the need for increased efforts to promote diversity and inclusivity in ophthalmology clinical trials. Ensuring equitable inclusion of different gender, racial, and ethnic groups in the trials is essential for minimizing disparities and producing unbiased scientific findings generalizable to the entire population. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.