Abstract Background Interest and participation in global health activities among U.S. medical trainees has increased sharply in recent decades, yet the global health activities of physicians who have completed residency training remain understudied. Our objectives were to assess associations between individual characteristics and patterns of post-residency global health activities across the domains of health policy, education, and research. Methods Cross-sectional, mixed methods national survey of 521 physicians with formal training in clinical and health services research and policy leadership. Main measures were post-residency global health activity and characteristics of this activity (location, funding, products, and perceived synergy with domestic activities). Results Most respondents (73%) hold faculty appointments across 84 U.S. medical schools and a strong plurality (46%) are trained in internal medicine. Nearly half of all respondents (44%) reported some global health activity after residency; however, the majority of this group (73%) reported spending ≤10% of professional time on global health in the past year. Among those active in global health, the majority (78%) reported receiving some funding for their global health activities, and most (83%) reported at least one scholarly, educational, or other product resulting from this work. Many respondents perceived synergies between domestic and global health activities, with 85% agreeing with the statement that their global health activities had enhanced the quality of their domestic work and increased their level of involvement with vulnerable populations, health policy advocacy, or research on the social determinants of health. Despite these perceived synergies, qualitative data from in-depth interviews revealed personal and institutional barriers to sustained global health involvement, including work-family balance and a lack of specific avenues for career development in global health. Conclusions Post-residency global health activity is common in this diverse, multi-specialty group of physicians. Although those with global health experience describe synergies with their domestic work, the lack of established career development pathways may limit the benefits of this synergy for individuals and their institutions.