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Objectives: The objective of this pilot study was to compare the effects of two mind-body interventions: mindfulness-based stress reduction (MBSR) and cognitive-behavioral stress reduction (CBSR). Subjects: Fifty ( 50) subjects were recruited from the community and took part in MBSR (n = 36) and CBSR (n = 14) courses. Participants self-selected into MBSR or CBSR courses taught at different times. There were no initial differences between the MBSR and CBSR subjects on demographics, including age, gender, education, and income. Intervention: MBSR was an 8-week course using meditation, gentle yoga, and body scanning exercises to increase mindfulness. CBSR was an 8-week course using cognitive and behavioral techniques to change thinking and reduce distress. Design: Perceived stress, depression, psychological well-being, neuroticism, binge eating, energy, pain, and mindfulness were assessed before and after each course. Pre-post scores for each intervention were compared by using paired t tests. Pre-post scores across interventions were compared by using a general linear model with repeated measures. Settings/Locations: Weekly meetings for both courses were held in a large room on a university medical center campus. Results: MBSR subjects improved on all eight outcomes, with all of the differences being significant. CBSR subjects improved on six of eight outcomes, with significant improvements on well-being, perceived stress, and depression. Multivariate analyses showed that the MBSR subjects had better outcomes across all variables, when compared with the CBSR subjects. Univariate analyses showed that MBSR subjects had better outcomes with regard to mindfulness, energy, pain, and a trend for binge eating. Conclusions: While MBSR and CBSR may both be effective in reducing perceived stress and depression, MBSR may be more effective in increasing mindfulness and energy and reducing pain. Future studies should continue to examine the differential effects of cognitive behavioral and mindfulness-based interventions and attempt to explain the reasons for the differences.