PURPOSE: This study examines the effect of coaching on errors and burnout on graduate medical education trainees and mechanisms of this effect. METHOD: In this explanatory, sequential, mixed-methods randomized controlled trial at a large, urban academic medical center, trainees and faculty were randomized to coaching with mentorship or mentorship alone from September 2021 to December 2022. Trainees randomized to coaching (coachees) were paired with faculty coaches from different specialties, who were trained in a novel coaching curriculum. Burnout was measured with the Stanford Professional Fulfillment Index subscales of professional fulfillment, work exhaustion, interpersonal disengagement, and overall burnout. Medical errors in the past 3 months were self-reported. Focus groups were conducted for each of the 4 cohorts (faculty control, faculty intervention, trainee control, and trainee intervention) to allow for an in-depth exploration of the coaching program experience. RESULTS: A total of 184 trainees and 150 faculty were randomized to standard mentorship with or without coaching. Paired analysis included 83 trainees (59% female) and 77 faculty (60% female). Difference-in-difference analyses showed reduced burnout among coachees compared with control trainees, with a score difference of -0.37 (95% CI, -0.64 to -0.09). Professional fulfillment improved in coachees, with a score difference of 0.50 (95% CI, 0.16-0.83) compared with control trainees. There were no significant differences in resilience or self-valuation. Coachees had 2.18 times greater odds of reporting no medical error than control trainees (not significant) and were less likely to report being "unsure" about medical error involvement. Qualitative analysis highlighted the importance of specialty discordance in coaching pairs and a coach's holistic awareness of coachee well-being and demonstrated successful uptake and use of coaching skills, particularly positive reframing and normalization. CONCLUSIONS: Coaching improved trainee burnout and professional fulfillment, likely through aspects of the relationship and teachable skills, which provided psychological safety and holistic support.