Background: Patients with panic disorder often suffer from temporary unavailability of care. The smartphone app Invirto (IVT) provides a digital treatment for panic disorder involving self-guided exposure in virtual reality. In this trial, we studied the efficacy of Invirto., Methods: In a randomized, controlled, non-blinded trial, we compared IVT with care as usual (CAU) in patients with panic disorder (pre-registration: DRKS00027585). The endpoints were assessed online before treatment (t0) and at three months (t1). The primary endpoint was a change in symptoms of anxiety as measured with the Beck Anxiety Inventory (BAI). The secondary endpoints were the patients' scores on the following assessment instruments, all in their German versions: the Panic and Agoraphobia Scale (PAS), the Beck Depression Inventory (BDI-II), a patient satisfaction questionnaire ( CSQ-8, Client-Satisfaction-Questionnaire), the Acceptance and Action Questionnaire (AAQ-II, in German FAH-II), and the quality of life as a global item in the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF)., Results: 124 patients were included in the trial. The intention-to-treat analysis revealed more pronounced improvement with IVT than with CAU with respect to both the primary (BAI, d = -0.46; 95% confidence interval [-0.87; -0.04]) and the secondary endpoints (PAS, d = -0.63 [-1.05; -0.22]; BDI-II, d = -0.44 [-0.86; -0.02]; FAH-II, d = -0.42 [-0.84; -0.01]), except the WHOQOL-BREF (p = 0.216)., Conclusion: A digital treatment with virtual exposure can lessen anxiety, panic, and depressive symptoms and improve mental flexibility. In further studies, IVT should be compared with an active control group.