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Despite significant psychosocial morbidity, there are few controlled trials of psychological support for people with brain tumor. This study evaluated the efficacy of the Making Sense of Brain Tumor (MSoBT) program, a home-based psychosocial intervention.A randomized controlled trial with a wait list conditionFifty participants aged 17–82 years with brain tumor (54% benign) were randomly allocated to immediate treatment (n= 27) or a waitlist (n= 23). Measures included Montgomery–Asberg Depression Rating Scale (MADRS), McGill Quality of Life (MQOL) Questionnaire, Depression Anxiety Stress Scales (DASS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). The immediate treatment group received the 10-session MSoBT program, while the waitlist group received usual care for 10 weeks and were then re-assessed before receiving the MSoBT program. A 6-month post-intervention follow-up was conducted.Analysis of covariance adjusting for baseline functioning identified that the immediate treatment group reported significantly lower levels of depression on the MADRS (ηp2 = .19) and higher levels of existential well-being on the MQOL (ηp2 = .13) and functional well-being (ηp2 = .21) and global quality of life on the FACT-Br (ηp2 = .12) at post-assessment than the waitlist group. At 6-month follow-up participants reported significantly lower levels of depression and stress and higher existential well-being and quality of life relative to pre-intervention.The MSoBT program appears to have efficacy for enhancing psychological well-being and quality of life after brain tumor. Copyright © 2014 John Wiley & Sons, Ltd.