Although there are multiple treatments for warts, wart management remains a challenge. Ozone therapy is an emerging treatment for infectious and noninfectious dermatological diseases.To assess intralesional ozone gas safety and efficacy in multiple warts management.Seventy-four adult patients with multiple common warts were included in this study. They were randomly assigned into 2 groups: first group comprised 44 patients treated with intralesional ozone gas, and the second group comprised 30 patients who received intralesional saline injection. In both groups, warts in all patients were directly injected weekly until complete clearance occurred or for a maximum of 10 treatment sessions. The subjects were followed for 6 months to record any recurrences.In the ozone group, 25 patients (56.8%) had a complete response with an excellent cosmetic outcome, 15 patients (34.1%) showed a partial response, and 4 patients (9.1%) had no response. More subjects responded to ozone than to saline (p < .001). Ozone therapy was associated with mild side effects, including pain at time of injection, numbness, and fatigue.Intralesional ozone is effective and safe for the treatment of multiple warts.