ABSTRACT: Patients who have received solid organ transplants continue to experience a myriad of complex symptoms related to their underlying disease and to chronic immunosuppression that reduce the quality of life. Beneficial nonpharmacologic therapies to address these symptoms have not been established in the transplant population.Assess the efficacy of mindfulness-based stress reduction (MBSR) in reducing symptoms of anxiety, depression, and poor sleep in transplant patients.Controlled trial with a two-staged randomization. Recipients of kidney, kidney/pancreas, liver, heart, or lung transplants were randomized to MBSR (n=72) or health education (n=66) initially or after serving in a waitlist. Mean age was 54 years (range 21-75); 55% were men, and 91% were white.MBSR, a mindfulness meditation training program consisting of eight weekly 2.5-hour classes; health education, a peer-led active control.Anxiety (State-Trait Anxiety Inventory), depression (Center for Epidemiologic Studies Depression Scale), and sleep quality (Pittsburgh Sleep Quality Index) scales assessed by self-report at baseline, 8 weeks, 6 months, and 1 year.Benefits of MBSR were above and beyond those afforded by the active control. MBSR reduced anxiety and sleep symptoms (P < .02), with medium treatment effects (.51 and .56) at 1 year compared to health education in intention-to-treat analyses. Within the MBSR group, anxiety, depression, and sleep symptoms decreased and quality-of-life measures improved by 8 weeks (P < .01, all), and benefits were retained at 1 year (P < .05, all). Initial symptom reductions in the health education group were smaller and not sustained. Comparisons to the waitlist confirmed the impact of MBSR on both symptoms and quality of life, whereas health education improvements were limited to quality-of-life ratings.MBSR reduced distressing symptoms of anxiety, depression, and poor sleep and improved quality of life. Benefits were sustained over 1 year. A health education program provided fewer benefits, and effects were not as durable. MBSR is a relatively inexpensive, safe, and effective community-based intervention.