Background: For unclear reasons, minorities have been historically underrepresented in multiple sclerosis (MS) clinical trials. We hypothesized that different perceptions and preferences about research participation among racial and ethnic groups contribute to this imbalance. Methods: Members of the MS Minority Research Engagement Partnership Network developed a Web-based survey in English and Spanish on research impressions, concerns, and preferences regarding study attributes among people with MS. Invitations to take the survey were distributed by network members and partner organizations. Results: We included 2599 participants with MS (2111 White, 215 African American; 188 Hispanic). Consistently disliked study attributes included potential harms to health and confusing study information. Compared with White and non-Hispanic participants, respectively, African American (odds ratio [OR] = 2.05, P ≤ .001) and Hispanic (OR = 1.79, P = .003) participants were more concerned about being used by the research team. Hispanic participants were more concerned about research participation carrying risks to their legal status (OR = 1.70, P = .001). Hispanic (OR = 3.18, P ≤ .001) and African American (OR = 5.51, P ≤ .001) participants were more likely to prefer for the study to benefit their own racial/ethnic group. A top concern across all groups was not being fully informed about the research. Conclusions: We found strong support for research across racial and ethnic groups; however, minority groups have specific concerns regarding mistrust, receiving poor-quality care, unemployment, health insurance, and legal status. Investigators wanting to recruit a diverse study population are advised to show how they have addressed these concerns and to communicate how the research will advance the science and literature and result in better care and/or other benefits to underrepresented communities.