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This study aimed to test the acceptability and effectiveness of a two-phase mindfulness-based stress reduction program (8-week initial treatment plus a 10-month maintenance phase) in alleviating work stress-related symptoms (i.e., burnout, heart rate [HR], and blood pressure [BP]) in a sample of 42 physicians.A randomized controlled trial and a simple pre-post design were used, respectively, for each of the two phases of the study. Outcome measures included the Five Facets of Mindfulness Questionnaire and the Maslach Burnout Questionnaire. HR and BP measures were also obtained in the experimental group by means of a digital monitor.After the initial 8 weeks of treatment, significant improvements for the experimental group in mindfulness levels and reductions in emotional exhaustion, HR, and BP were obtained. Effect sizes (Cohen d) significantly increased over the 10-month maintenance period, especially for mindfulness and systolic BP. Acceptance was notably high (low attrition rate and high compliance with program activities).Outcomes are significant in terms of practical consequences for reducing and controlling risks of developing burnout and cardiovascular disease in this population and enhancing well-being in life.