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Context  Primary care physicians report high levels of distress, which is linked to burnout, attrition, and poorer quality of care. Programs to reduce burnout before it results in impairment are rare; data on these programs are scarce.Objective  To determine whether an intensive educational program in mindfulness, communication, and self-awareness is associated with improvement in primary care physicians' well-being, psychological distress, burnout, and capacity for relating to patients.Design, Setting, and Participants  Before-and-after study of 70 primary care physicians in Rochester, New York, in a continuing medical education (CME) course in 2007-2008. The course included mindfulness meditation, self-awareness exercises, narratives about meaningful clinical experiences, appreciative interviews, didactic material, and discussion. An 8-week intensive phase (2.5 h/wk, 7-hour retreat) was followed by a 10-month maintenance phase (2.5 h/mo).Main Outcome Measures  Mindfulness (2 subscales), burnout (3 subscales), empathy (3 subscales), psychosocial orientation, personality (5 factors), and mood (6 subscales) measured at baseline and at 2, 12, and 15 months.Results  Over the course of the program and follow-up, participants demonstrated improvements in mindfulness (raw score, 45.2 to 54.1; raw score change [Δ], 8.9; 95% confidence interval [CI], 7.0 to 10.8); burnout (emotional exhaustion, 26.8 to 20.0; Δ = −6.8; 95% CI, −4.8 to −8.8; depersonalization, 8.4 to 5.9; Δ = −2.5; 95% CI, −1.4 to −3.6; and personal accomplishment, 40.2 to 42.6; Δ = 2.4; 95% CI, 1.2 to 3.6); empathy (116.6 to 121.2; Δ = 4.6; 95% CI, 2.2 to 7.0); physician belief scale (76.7 to 72.6; Δ = −4.1; 95% CI, −1.8 to −6.4); total mood disturbance (33.2 to 16.1; Δ = −17.1; 95% CI, −11 to −23.2), and personality (conscientiousness, 6.5 to 6.8; Δ = 0.3; 95% CI, 0.1 to 5 and emotional stability, 6.1 to 6.6; Δ = 0.5; 95% CI, 0.3 to 0.7). Improvements in mindfulness were correlated with improvements in total mood disturbance (r = −0.39, P < .001), perspective taking subscale of physician empathy (r = 0.31, P < .001), burnout (emotional exhaustion and personal accomplishment subscales, r = −0.32 and 0.33, respectively; P < .001), and personality factors (conscientiousness and emotional stability, r = 0.29 and 0.25, respectively; P < .001).Conclusions  Participation in a mindful communication program was associated with short-term and sustained improvements in well-being and attitudes associated with patient-centered care. Because before-and-after designs limit inferences about intervention effects, these findings warrant randomized trials involving a variety of practicing physicians.