Puerto Ricans are underrepresented in genetic research. This underrepresentation denies Puerto Ricans the benefit from therapeutic developments that could mitigate health disparities arising from conditions for which genetically-derived treatments exist. The Puerto Rican diaspora, especially post-2017 due to economic and environmental crises, has expanded within the USA. Prior research suggests that Latin American diaspora communities are less likely to participate in genetic research. We hypothesized, specifically, that the Puerto Rican diaspora in the USA would be less likely to participate in genetic research than would Puerto Ricans in their homeland's archipelago, and that accounting for social and cultural determinants related to the diaspora experience would mitigate this disparity. We implemented an analytical cross-sectional study of archipelago-residing Puerto Ricans and of the USA-residing diaspora to evaluate this hypothesis. With 1582 Puerto Ricans (723 in Puerto Rico, 859 in the USA), we found that while most participants would participate in genetic research, participation rates varied significantly by diaspora status. Puerto Ricans born and living in the USA were initially more likely to decline participation compared to those in Puerto Rico (OR = 1.54, p < 0.01). However, once adjusted for social and cultural variables, this difference was eliminated (aOR = 1.08, p = n.s.). The factors influencing non-participation include oppression, discrimination, distrust, and social determinants, aligning with the theory of minoritization. An important community in the USA and in the world, Puerto Ricans have the right to participate in well-conducted research and to benefit from its findings, particularly around topics that could help address existing disparities in health outcomes.