Background/Aims: Recent genomic medicine initiatives underscore the importance of including diverse participants in research. Considerable literature has identified barriers to and facilitators of increasing diversity, yet disparities in recruiting and retaining adequate numbers of participants from diverse groups continue to limit the generalizability of clinical genomic research. Methods: The North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing study employed evidence-based strategies to enhance the participation of under-represented minority patients. In this study, we evaluate the impact of our efforts by systematically analyzing the “cascade” of attrition of participants throughout study interactions. Results: Although successful in recruiting a cohort that included ~30% non-Caucasian patients overall, the study still enrolled and retained a lower proportion of minorities compared to the pool of eligible patients who were nominated. We evaluated sociodemographic characteristics and related variables as potential factors associated with attrition throughout these phases of the study. Conclusions: These results suggest that varied approaches will be needed to increase participation in genomic medicine research. Our findings highlight factors to consider when developing strategies to address this critical need. Failing to include a broad range of populations in research studies will exacerbate existing disparities in the translation of genomic sequencing to medical care.