OBJECTIVES: To compare the clinical effectiveness of the virtual reality (VR) programs in assessing psychosocial problems, improving symptoms, and reducing suicide risk in depressive patients with those of pharmacotherapy. METHODS: Thirty-six patients were recruited with depression in the treatment group and 22 participants in the healthy control group through internet advertisements between November 2018 and March 2019. Participants in the treatment group were allocated randomly at a 1:1 ratio to either the VR group or pharmacotherapy group. At the baseline, all participants were assessed with a comprehensive battery for their psychological characteristics by structured scales using VR technologies. Assessments of patients in the treatment group were repeated four weeks after therapeutic intervention. The primary outcome measures were the Korean Version of Quick Inventory of Depressive Symptomatology-Self-Report and suicidality scales of the Korean Mini International Neuropsychiatric interview. The borderline personality (Personality Assessment Inventory-Borderline Features Scale) and resilience (Korean Resilience Questionnaire) were also evaluated. RESULTS: Twenty-four depressive patients completed the treatment, and the final assessment was conducted after four weeks of treatment. In the initial assessment, the patient group showed significantly higher depressive symptoms, suicidality, borderline personality trait, and lower resilience than healthy control group. After the four-week therapeutic interventions, the VR group showed significant improvement in depression, suicidality, borderline personality trait, and resilience. In addition, there was no significant difference in the treatment efficacy between the VR group and the pharmacotherapy group. CONCLUSION In this study, the VR treatment program has clear benefits for emotional distress and reducing suicidality in depressive patients. Evidence-based VR treatments may show new clinical potential for depressive disorder.