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Background Positive effects of mind-body skills programs on participant well-being have been reported in health professions students. The success seen with medical students at this university led to great interest in expanding the mind-body skills program so students in other disciplines could benefit from the program. Objective The purpose of this study was to assess the effects of a 9-week mind-body skills program on the mental and emotional well-being of multidisciplinary students compared to controls. We also sought to determine if the program’s effects were sustained at 1-year follow-up. Methods A cross-sectional pre-post survey was administered online via SurveyMonkey to participants of a 9-week mind-body skills program and a control group of students from 7 colleges at a public university from 2017–2019. Students were assessed on validated measures of stress, positive/negative affect, resilience, depression, anxiety, fatigue, sleep disturbance, mindfulness, empathy, and burnout. Scores were analyzed between-groups and within-groups using bivariate and multivariate analyses. A 1-year follow-up was completed on a subset of participants and controls. Results 279 participants and 247 controls completed the pre-survey and post-survey (79% response rate; 71% female, 68% white, mean age = 25 years). Participants showed significant decreases in stress, negative affect, depression, anxiety, sleep disturbance, and burnout, while positive affect, resilience, mindfulness, and empathy increased significantly ( P <  .05). Only sleep disturbance showed a significant decrease in the control group. Follow-up in a subset of participants showed that only mindfulness remained elevated at 1-year ( P <  .05), whereas the significant changes in other well-being measures were not sustained. Conclusion Participation in a 9-week mind-body skills program led to significant improvement in indicators of well-being in multidisciplinary students. A pilot 1-year follow-up suggests that effects are only sustained for mindfulness, but not other parameters. Future programming should focus on implementing mind-body skills booster sessions to help sustain the well-being benefits.