PURPOSE: To assess safety and effectiveness of computed tomography (CT)-guided intradiscal oxygen-ozone therapy (O(2)-O(3) therapy) for the treatment of symptomatic lumbar disc herniation and radiological changes. MATERIALS AND METHODS: This study was conducted in twenty patients presenting lumbar disc herniation with resistant lumbar or lumbar radicular pain They underwent intradiscal oxygen-ozone therapy under CT guidance. They were treated at one- or two-disc levels, representing a total of 24 discs treated. MR imaging examinations were obtained before treatment and 2 months post-procedure to analyse treatment-related disc modifications including modification of the surfaces of the disc and of the herniated disc, and the variations in disc height according to the disc height index. Clinical outcomes were assessed using the visual analogue scale (VAS) to evaluate the severity of pain before the procedure, at primary (2 months) and at secondary (12 months) follow-ups. RESULTS: All the procedures were technically successful. The median VAS scores were 7.95 before the procedure, 3.9 at 2 months and 2.95 at 12 months. MRI analysis showed a significant decrease in herniation size at 2 months (-20%, p = 0.008). No immediate or late complications were observed. Only three patients (13.6%) underwent lumbar spine microdiscectomy in the year following ozone therapy. The treatment appeared to be more effective in cases of nerve root symptomatology. CONCLUSION: This study suggests that intradiscal O(2)-O(3) therapy is safe and effective for the treatment of lumbar disc herniation associated with resistant lumbar or lumbar radicular pain.