Importance Among surgical trainees, burnout and distress are prevalent, but mindfulness has been shown to decrease the risk of depression, suicidal ideation, burnout, and overwhelming stress. In other high-stress populations, formal mindfulness training has been shown to improve mental health, yet this approach has not been tried in surgery. Objective To test the feasibility and acceptability of modified Mindfulness-Based Stress Reduction (MBSR) training during surgical residency. Design, Setting, and Participants A pilot randomized clinical trial of modified MBSR vs an active control was conducted with 21 surgical interns in a residency training program at a tertiary academic medical center, from April 30, 2016, to December 2017. Interventions Weekly 2-hour, modified MBSR classes and 20 minutes of suggested daily home practice over an 8-week period. Main Outcomes and Measures Feasibility was assessed along 6 domains (demand, implementation, practicality, acceptability, adaptation, and integration), using focus groups, interviews, surveys, attendance, daily practice time, and subjective self-report of experience. Results Of the 21 residents included in the analysis, 13 were men (62%). Mean (SD [range]) age of the intervention group was 29.0 (2.4 [24-31]) years, and the mean (SD [range]) age of the control group was 27.4 (2.1 [27-33]) years. Formal stress-resilience training was feasible through cultivation of stakeholder support. Modified MBSR was acceptable as evidenced by no attrition; high attendance (12 of 96 absences [13%] in the intervention group and 11 of 72 absences [15%] in the control group); no significant difference in days per week practiced between groups; similar mean (SD) daily practice time between groups with significant differences only in week 1 (control, 28.15 [12.55] minutes; intervention, 15.47 [4.06] minutes;P = .02), week 2 (control, 23.89 [12.93] minutes; intervention, 12.61 [6.06] minutes;P = .03), and week 4 (control, 26.26 [13.12] minutes; intervention, 15.36 [6.13] minutes;P = .04); course satisfaction (based on interviews and focus group feedback); and posttraining-perceived credibility (control, 18.00 [4.24]; intervention, 20.00 [6.55];P = .03). Mindfulness skills were integrated into personal and professional settings and the independent practice of mindfulness skills continued over 12 months of follow-up (mean days [SD] per week formal practice, 3 [1.0]). Conclusions and Relevance Formal MBSR training is feasible and acceptable to surgical interns at a tertiary academic center. Interns found the concepts and skills useful both personally and professionally and participation had no detrimental effect on their surgical training or patient care. Trial Registration ClinicalTrials.gov identifier:NCT03141190