Young adults from underserved racial/ethnic groups are critically needed as unrelated hematopoietic stem cell (HSC) donors, yet they are more likely than other groups to opt out of donation after having matched a patient. Understanding which factors are most strongly associated with opting out among young underserved racial/ ethnic registered donors compared with their White counterparts will provide the basis for specific interventions to improve donor retention. We sought to determine the key, modifiable psychosocial, registry-related, and donation-related characteristics that are uniquely associated with opting out across 5 key racial/ethnic groups of young HSC donor registry members who had been contacted as a potential match for a patient. This study examines data from a large cross-sectional survey of young (age 18 to 30) registry members shortly after they preliminarily matched a patient (CT-stage) and continued toward or opted out of donation (CT-C and CT-NI), stratified by racial/ethnic group and sex. We assessed psychosocial, registry-related, and donation-related characteristics for all participants. We used chi-squared and F tests to assess differences between racial/ethnic groups. A separate logistic regression analysis for each racial/ethnic group was conducted to quantify adjusted associations between each variable and opting out. Then, we compared these associations across the racial/ethnic groups by evaluating the interaction effect between each variable and racial/ethnic group, with the same outcome (CT-C versus CT-NI) in question. Nine hundred thirty-five participants were surveyed, including 284 White, 165 Hispanic, 191 Black, 192 Asian/Pacific Islander, and 103 Multiracial/multiethnic participants. There were significant differences across racial/ethnic groups in values/goals, religious objections to donation, HSC-related medical mistrust, and parental involvement in donation decisions. Adjusted logistic regression subgroup analyses indicated that ambivalence was strongly associated with opting out across all racial/ethnic groups. Greater focus on intrinsic life goals (e.g., raising a family, becoming a community leader, influencing social values) was associated with opting out in the Multiracial/multiethnic, Hispanic, and Asian/Pacific Islander groups. Healthcare mistrust and insufficient registry contact was a significant factor for Hispanic participants. Protective factors against opting out included remembering joining the registry (Black participants), and parental support for donation decision (Asian/Pacific Islander participants). The performance of each logistic regression model was strong, with area-under-the curve ≥.88, CT-stage outcome classification accuracy ≥89%, and good fit between expected and observed opt-out probabilities. In the analysis across different racial/ethnic groups, the only significant interaction was race/ethnicity by whether more contact with the registry would have changed the decision at CT-stage; this variable was significant only for the Hispanic group. In the within-group analysis for Hispanic participants, the "more registry contact" variable was strongly associated with opting out (odds ratio 5.8, P = .03). Consistent with a growing body of HSC donor research, ambivalence was a key factor associated with opting-out for all racial/ethnic groups. Other key variables were differentially associated with opting-out depending on racial/ethnic group. Our study highlights key variables that registries should focus on as they develop targeted and tailored strategies to enhance commitment and reduce attrition of potential donors.