Purpose Mentored K (K01/K08/K23) career development awards are positively associated with physicians' success as independent investigators; however, individuals in some racial/ethnic groups are less likely to receive this federal funding. The authors sought to identify variables that explain (mediate) the association between race/ethnicity and mentored K award receipt among U.S. Liaison Committee for Medical Education-accredited medical school graduates who planned research-related careers. Method The authors analyzed deidentified data from the Association of American Medical Colleges and the National Institutes of Health Information for Management, Planning, Analysis, and Coordination II grants database for a national cohort of 28,690 graduates from 1997-2004 who planned research-related careers, followed through August 2014. The authors examined 10 potential mediators (4 research activities, 2 academic performance measures, medical school research intensity, degree program, debt, and specialty) of the association between race/ethnicity and mentored K award receipt in models comparing underrepresented minorities in medicine (URM) and non-URM graduates. Results Among 27,521 graduates with complete data (95.9% of study-eligible graduates), 1,147 (4.2%) received mentored K awards (79/3,341 [2.4%] URM; 1,068/24,180 [4.4%] non-URM). All variables except debt were significant mediators; together they explained 96.2% (95%, CI 79.1%-100%) of the association between race/ethnicity and mentored K award. Conclusions Research-related activities during/after medical school and standardized academic measures largely explained the association between race/ethnicity and mentored K award in this national cohort. Interventions targeting these mediators could mitigate racial/ethnic disparities in the federally funded physician-scientist research workforce.