Objective: To investigate the efficacy of add-on mantra meditation compared to progressive muscle relaxation in major depression. Methods: This study was a two-arm, single-site, raterblinded, randomized controlled trial involving 123 inpatients at a psychiatric hospital diagnosed with major depression according to DSM-IV criteria (January 2017 to June 2020). The treatment group practiced mantra meditation (MAM, N = 60); the comparator group practiced progressive muscle relaxation (PMR, N = 63). Both treatments were delivered via an introductory lesson followed by 30-minute group sessions twice weekly, adjunctively to usual treatment for depressive inpatients (TAU). The primary outcome measure was change in clinician-rated depression symptom severity, measured by the MADRS interview. The secondary outcome measure was self-reported depression severity, measured by the BDI-II questionnaire. Intentionto-treat was analyzed using linear mixed models. Results: The TAU + MAM group had significantly greater improvements in MADRS score than the TAU + PMR group, both at the 3- month follow-up (between-group difference = 4.78, 95% CI = -8.32 – -1.42; d = 0.62) and at the 6-month follow-up (between-group difference = -6.24, 95% CI = -9.80 – -2.69; d = 0.79). Posttreatment, self-reported depression symptom severity was not significantly lower in the TAU + MAM group than in the TAU + PMR group. Exploratory analysis of the differences between primary and secondary outcomes showed that mantra meditation mainly improved mood rather than cognitive symptoms. Conclusions: In inpatients with major depression, adjunctive mantra meditation led to clinically relevant reduction in depressive symptom severity. Further research would build evidence for the untapped potentials of mantra meditation. ClinicalTrials.gov