BACKGROUND: Medical students have high levels of stress, which is associated with higher incidents of burnout, depression, and suicide compared to age-matched peers. Mindfulness practices have been shown to reduce stress among medical students. PURPOSE: The purpose of this systematic review and meta-analysis was to examine if mindfulness interventions have an overall effect on stress outcomes in the high-stress population of medical students globally, particularly given the wide variety of interventions. Any intervention designed to promote mindfulness was included. METHODS: A comprehensive literature search was completed to include multiple databases, ancestry, and hand-searching and 35 studies were included. Standardized mean difference effect sizes (ES) were synthesized across studies using a random-effects model for changes in stress levels in medical students ≥ 18. Moderator analyses were performed to explore variations in effects by participant and intervention characteristics. RESULTS: Mindfulness interventions significantly improved stress among medical students in both the two-arm studies (d = 0.370, k = 19, n = 2,199, 95% CI 0.239-0.501, p < .001) and one-arm pre-post studies (d = 0.291, k = 30, n = 18 (two cohorts from Dyrbye et al), 95% CI 0.127-0.455, p = 0.001). Moderator analyses found trends in less hours and less required practice resulted in better improvement in stress. CONCLUSIONS: This study further confirms that despite a wide variety of mindfulness interventions for medical students around the world, they produce an overall small-to-moderate effect on stress reduction. Future research looking at the most effective protocols for high-stress medical students would be beneficial.