Objective: To evaluate the association between degree of professional burnout and physicians' sense of calling., Participants and Methods: US physicians across all specialties were surveyed between October 24, 2014, and May 29, 2015. Professional burnout was assessed using a validated single-item measure. Sense of calling, defined as committing one's life to personally meaningful work that serves a prosocial purpose, was assessed using 6 validated true-false items. Associations between burnout and identification with calling items were assessed using multivariable logistic regressions., Results: A total of 2263 physicians completed surveys (63.1% response rate). Among respondents, 28.5% (n=639) reported experiencing some degree of burnout. Compared with physicians who reported no burnout symptoms, those who were completely burned out had lower odds of finding their work rewarding (odds ratio [OR], 0.05; 95% CI, 0.02-0.10; P<.001), seeing their work as one of the most important things in their lives (OR, 0.38; 95% CI, 0.21-0.69; P<.001), or thinking their work makes the world a better place (OR, 0.38; 95% CI, 0.17-0.85; P=.02). Burnout was also associated with lower odds of enjoying talking about their work to others (OR, 0.23; 95% CI, 0.13-0.41; P<.001), choosing their work life again (OR, 0.11; 95% CI, 0.06-0.20; P<.001), or continuing with their current work even if they were no longer paid if they were financially stable (OR, 0.30; 95% CI, 0.15-0.59; P<.001)., Conclusion: Physicians who experience more burnout are less likely to identify with medicine as a calling. Erosion of the sense that medicine is a calling may have adverse consequences for physicians as well as those for whom they care., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)