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6 reviewsParanoia is a distressing and prevalent symptom in schizophrenia spectrum disorders. Virtual reality-based cognitive behavioral therapy for paranoia (VR-CBTp) has been proposed to augment behavioral interventions by providing controlled and safe virtual environments in which social situations inducing paranoid anxiety can be manipulated, allowing for new therapeutical possibilities such as gradual exposure and repetition. This assessor-masked, randomized parallel group superiority trial investigated the efcacy of VR-CBTp compared to standard CBTp. Participants were randomized to receive ten sessions of VR-CBTp or CBTp, both on top of treatment as usual. Intention-to-treat analyses included 254 participants (VR-CBTp: n = 126, CBTp: n = 128). Outcomes were assessed at baseline, treatment cessation and follow-up (6 months after treatment cessation). The primary outcome was Ideas of Persecution subscale from the Green Paranoid Thoughts Scale, measured at treatment cessation. There was not a statistically signifcant between-group diference on the primary outcome at endpoint (efect estimate: 2% in favor of VR-CBTp; 95% confdence interval: −11% to +17%; Cohen’s d = 0.04; P = 0.77, based on exponentiated log-transformed data). No deaths or violent incidents involving law enforcement occurred during the study. In conclusion, VR-CBTp was not superior to CBTp in reducing schizophrenia-spectrum-disordersrelated paranoia. ClinicalTrials.gov registration: NCT04902066.