Background: Oxygen-ozone therapy is a minimally invasive treatment for lumbar disc herniation that exploits the biochemical properties of a gas mixture of oxygen and ozone. Objective: The purpose of our study was to prospectively evaluate the clinical effectiveness of oxygenozone therapy and compared the therapeutic outcome of injection of oxygen-ozone combined steroid with injection of steroid alone at different follow-up period. Patients and Methods: One hundred patients were included for this study from al-Agouza Physical Medicine, Rheumatology and Rehabilitation center. From March 2014 to April 2016, we treated 100 patients (42 men, 58 women; age range, 23–65 years) with lumbar disk herniation (L3-4, 23 patients; L4-5, 61 patients; L5-S1, 75 patients) and radicular pain. The mean duration of radicular pain at the time of treatment was 8 weeks. Result: Satisfactory clinical outcomes were obtained in both groups after two weeks, three months and at 6 months. Treatment was successful in patients in group I and patients in group II. The difference between group I and group II was insignificant. Conclusion: O2–O3 seems to play a role in pain relief, and we suggest the administration of the O2– O3 mixture combined with transforaminal steroid injection as a first-choice treatment before recourse to surgery or when surgery is not possible.