PURPOSE: Medical students have higher rates of depression and psychologic distress than the general population, which may negatively impact academic performance and professional conduct. This study assessed whether 10-20 min of daily mindfulness meditation for 30 days, using a mobile phone application, could decrease perceived stress and improve well-being for medical students. METHODS: Eighty-eight medical students were stratified by class year and randomized to either intervention or control groups to use the mobile application Headspace, an audio-guided mindfulness meditation program, for 30 days. All participants completed the Perceived Stress Scale (PSS), Five-Facet Mindfulness Questionnaire (FFMQ), and General Well-Being Schedule (GWBS) at baseline (T1), 30 days (T2), and 60 days (T3). Repeated measures analysis of variance (rANOVA) was conducted for intervention versus control groups across T1, T2, and T3 to examine differences in stress, mindfulness, and well-being. RESULTS: There was a significant interaction between time and treatment group for perceived stress and well-being. Perceived stress significantly decreased for the intervention group from T1 to T3 (F[2,142] = 3.98, p < 0.05). General well-being significantly increased for the intervention group compared to the control group from T1 to T2, and the increase was sustained through T3 (F[2,144] = 3.36, p < 0.05). CONCLUSIONS: These results highlight that a mobile audio-guided mindfulness meditation program is an effective means to decrease perceived stress in medical students, which may have implications on patient care. Integrating mindfulness training into medical school curricula for management of school- and work-related stress may lead to fewer negative physician outcomes (e.g., burnout, anxiety, and depression) and improved physician and patient outcomes. This has implications for a broad group of therapists and healthcare providers, ultimately improving quality of healing and patient care.