BACKGROUND: Patients with progressive kidney disease experience increasing physiologic and psychosocial stressors and declining health-related quality of life (HRQOL). METHODS: We conducted a randomized, active-controlled, open-label trial to test whether a Mindfulness-based Stress Reduction (MBSR) program delivered in a novel workshop-teleconference format would reduce symptoms and improve HRQOL in patients awaiting kidney transplantation. Sixty-three transplant candidates were randomized to one of two arms: i) telephone-adapted MBSR (tMBSR, an 8-week program of meditation and yoga); or ii) a telephone-based support group (tSupport). Participants completed self-report questionnaires at baseline, post-intervention, and after 6-months. Anxiety, measured by the State-Trait Anxiety Inventory (STAI) post-intervention served as the primary outcome. Secondary outcomes included: depression, sleep quality, pain, fatigue, and HRQOL assessed by SF-12 Physical and Mental Component Summaries (PCS, MCS). RESULTS: 55 patients (age 54±12yrs) attended their assigned program (tMBSR, n=27; tSupport, n=28). 49% of patients had elevated anxiety at baseline. Changes in anxiety were small and did not differ by treatment group post-intervention or at follow-up. However, tMBSR significantly improved mental HRQOL at follow-up: +6.2 points on the MCS - twice the minimum clinically important difference (95% CI: 1.66 to 10.8, P=0.01). A large percentage of tMBSR participants (≥90%) practiced mindfulness and reported it helpful for stress management. CONCLUSIONS: Neither mindfulness training nor a support group resulted in clinically meaningful reductions in anxiety. In contrast, finding that tMBSR was more effective than tSupport for bolstering mental HRQOL during the wait for a kidney transplant is encouraging and warrants further investigation. ClinicalTrials.govNCT01254214.