This study sought to identify the association between rates of burnout and career choice regret amongst resident physicians and whether this varies by clinical specialty. A prospective cohort study was conducted in which US resident physicians completed baseline questionnaires during their fourth year of medical school and then during their second year of residency. Exposures that were measured through the questionnaires included clinical specialty, demographics, educational debt, US Medical Licensing Examination Step 1 scores, and reported levels of anxiety, empathy, and social support. Results found that symptoms of burnout and career choice regret were prevalent amongst physicians, and were relatively higher within the fields of urology, neurology, emergency medicine, ophthalmology, and general surgery.