BACKGROUND: Many resident physicians suffer from distress, which endangers their individual health and the quality of care. OBJECTIVE: To examine the impact of a tailored mindfulness-based program (MBP) for resident physicians on distress and the quality of care. METHODS: A single-centre, two-armed, longitudinal randomised controlled trial. The intervention group took part in an 8-week, tailored MBP that included a coursebook. The MBP was followed by a 4-month maintenance phase. The active control group received the coursebook for self-study. Assessments were at baseline (t0, 0 months), after the intervention (t1, 2 months), after the maintenance phase (t2, 6 months), and at follow-up (t3, 12 months). The primary outcome was a change in burnout at t2. Secondary outcomes included perceived stress, mental distress, perceived job strain, depression, anxiety, hair cortisol secretion, self-reported medical errors and third-party ratings by patients, supervisors and colleagues. RESULTS: Seventy-six participants were randomised to the intervention and 71 to the control group. The intervention group showed greater improvements in the primary outcome (burnout at t2, d = 0.32, p = 0.046), in perceived stress (d = 0.31, p = 0.046) and perceived job strain (d = 0.33, p = 0.026) at t1, and in supervisor rated empathy (d = 0.71, p = 0.037) and colleague rated attentiveness (d = 0.85, p = .006) at t2. There was no difference between groups in the other outcomes. CONCLUSION: A tailored MBP for resident physicians improved burnout and might have improved other aspects of distress and the quality of care.