OBJECTIVE Burnout symptoms among physicians are common and have potentially serious ramifications for physicians and their patients. Randomized studies testing interventions to address burnout have been uncommon. OBJECTIVE To explore the effect of individualized coaching on the well-being of physicians. METHODS A pilot randomized clinical trial involving 88 practicing physicians in the departments of medicine, family medicine, and pediatrics who volunteered for coaching was conducted between October 9, 2017, and March 27, 2018, at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Statistical analysis was conducted from August 24, 2018, to March 25, 2019. METHODS A total of 6 coaching sessions facilitated by a professional coach. METHODS Burnout, quality of life, resilience, job satisfaction, engagement, and meaning at work using established metrics. Analysis was performed on an intent-to-treat basis. RESULTS Among the 88 physicians in the study (48 women and 40 men), after 6 months of professional coaching, emotional exhaustion decreased by a mean (SD) of 5.2 (8.7) points in the intervention group compared with an increase of 1.5 (7.7) points in the control group by the end of the study (P < .001). Absolute rates of high emotional exhaustion at 5 months decreased by 19.5% in the intervention group and increased by 9.8% in the control group (-29.3% [95% CI, -34.0% to -24.6%]) (P < .001). Absolute rates of overall burnout at 5 months also decreased by 17.1% in the intervention group and increased by 4.9% in the control group (-22.0% [95% CI, -25.2% to -18.7%]) (P < .001). Quality of life improved by a mean (SD) of 1.2 (2.5) points in the intervention group compared with 0.1 (1.7) points in the control group (1.1 points [95% CI, 0.04-2.1 points]) (P = .005), and resilience scores improved by a mean (SD) of 1.3 (5.2) points in the intervention group compared with 0.6 (4.0) points in the control group (0.7 points [95% CI, 0.0-3.0 points]) (P = .04). No statistically significant differences in depersonalization, job satisfaction, engagement, or meaning in work were observed. CONCLUSIONS Professional coaching may be an effective way to reduce emotional exhaustion and overall burnout as well as improve quality of life and resilience for some physicians. BACKGROUND ClinicalTrials.gov identifier: NCT03207581.