This longitudinal study in Mayo Clinic Proceedings evaluated the relationship between burnout and professional satisfaction with changes in physicians’ professional effort. Administrative/payroll records were used to longitudinally evaluate the professional work effort of faculty physicians working for Mayo Clinic from October 1, 2008, to October 1, 2014, and physicians were longitudinally surveyed in October 2011 and October 2013 with standardized tools to assess burnout and satisfaction. Results indicated that burnout and declining satisfaction were strongly associated with actual reductions in professional work effort over the following 24 months.