Background: Schizophrenia spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of cognitive behavioral therapy (CBT) for psychosis show small to moderate effect sizes in reducing paranoid ideations. Virtual reality-based CBT (VR-CBT) could improve therapy efficacy as exposure and behavioral experiments in VR can be optimized, individualized, and carried out in a safe environment. Few VR-CBT studies exist for paranoid ideations and there is a need for large-scale, methodologically rigorous trials. Methods: This study is a randomized, assessor-blinded parallel-groups multi-center superiority clinical trial, fulfilling the CONSORT criteria for non-pharmacological treatment. A total of 256 patients diagnosed with schizophrenia spectrum disorder, including schizotypal disorder (ICD-10 F20-29), will be allocated to either 10 sessions of symptom-specific CBT-VR plus treatment as usual—versus 10 sessions of standard symptom-specific CBT for paranoid ideations (CBT) plus treatment as usual. All participants will be assessed at baseline, treatment end (3 months post baseline), and then 9 months post baseline. A stratified block-randomization with concealed randomization sequence will be conducted. Independent assessors blinded to the treatment will evaluate the outcome. Analysis of outcome will be carried out with the intention to treat principles. The primary outcome is ideas of social reference measured with Green Paranoid Thought Scale Part A (GPTS-A) at the cessation of treatment at 3 months post baseline. Secondary outcomes are ideas of persecution (GPTS-B), Social Interaction Anxiety Scale (SIAS), Personal and Social Performance scale (PSP), Safety Behavior Questionnaire (SBQ), and CANTAB Emotion Recognition Task. Discussion: The trial will elucidate whether VR-CBT can enhance therapy efficacy for paranoid ideations. Additionally, Trial findings will provide evidence on the effectiveness and cost-effectiveness of VR-CBT for paranoid ideations that can guide the possible dissemination and implementation into clinical practice. Trial registration: ClinicalTrials.govNCT04902066. Initial release April 9th, 2021.