Background: Cognitive behavioral therapy (CBT) is the current standard treatment for chronic severe tinnitus; however, preliminary evidence suggests that real-time functional MRI (fMRI) neurofeedback therapy may be more effective. Purpose: To compare the efficacy of real-time fMRI neurofeedback against CBT for reducing chronic tinnitus distress. Materials and Methods: In this prospective controlled trial, participants with chronic severe tinnitus were randomized from December 2017 to December 2021 to receive either CBT (CBT group) for 10 weekly group sessions or real-time fMRI neurofeedback (fMRI group) individually during 15 weekly sessions. Change in the Tinnitus Handicap Inventory (THI) score (range, 0-100) from baseline to 6 or 12 months was assessed. Secondary outcomes included four quality -of -life questionnaires (Beck Depression Inventory, Pittsburgh Sleep Quality Index, State -Trait Anxiety Inventory, and World Health Organization Disability Assessment Schedule). Questionnaire scores between treatment groups and between time points were assessed using repeated measures analysis of variance and the nonparametric Wilcoxon signed rank test. Results: The fMRI group included 21 participants (mean age, 49 years +/- 11.4 [SD]; 16 male participants) and the CBT group included 22 participants (mean age, 53.6 years +/- 8.8; 16 male participants). The fMRI group showed a greater reduction in THI scores compared with the CBT group at both 6 months (mean score change, -28.21 points +/- 18.66 vs -12.09 points +/- 18.86; P = .005) and 12 months (mean score change, -30 points +/- 25.44 vs -4 points +/- 17.2; P = .01). Compared with baseline, the fMRI group showed improved sleep (mean score, 8.62 points +/- 4.59 vs 7.25 points +/- 3.61; P = .006) and trait anxiety (mean score, 44 points +/- 11.5 vs 39.84 points +/- 10.5; P = .02) at 1 month and improved depression (mean score, 13.71 points +/- 9.27 vs 6.53 points +/- 5.17; P = .01) and general functioning (mean score, 24.91 points +/- 17.05 vs 13.06 points +/- 10.1; P = .01) at 6 months. No difference in these metrics over time was observed for the CBT group (P value range, .14 to >.99). Conclusion: Real-time fMRI neurofeedback therapy led to a greater reduction in tinnitus distress than the current standard treatment of CBT. (c) RSNA, 2024