We prospectively assessed the diagnostic criteria of morphologic MRI study (MMS) and the accuracy of DWI and related ADC values (DWI-ADC) versus intervertebral disk volumetric analysis (IDVA) for predicting shrinkage of lumbar disk herniation treated with oxygen-ozone (O2-O3) diskolysis. Sixty-eight patients (36 men and 32 women; mean age 39) with lumbosciatica underwent O2-O3 diskolysis. The six-month MRI follow-up was performed with FSE-T2 and T2-fat, SE-T1 and DWI-weighted images. IDVA was determined using OsiriX(®). Diagnostic criteria and accuracy were evaluated with regards to DWI and related ADC in detecting response to ozone therapy. Fifty-eight of 68 patients had successful outcomes (responders), whereas ten patients showed unsatisfactory outcomes (non-responders). MMS showed that a centrally located herniated disk and grade 1 nerve root compression were more common in the responder group (p < 0.05). DWI-ADC and IDVA showed statistically significant shrinkage in the sixth month of follow-up (p < 0.05) with a mean ADC value reduction of 2.10 × 10(-3) mm(2)/s +/- 0.19 SD in the second month of follow-up (p < 0.05). DWI-ADC had an accuracy of 0.81 in detecting response to therapy around the second month of follow-up. DWI-ADC appear to be useful adjuncts to MMS in the follow-up of patients undergoing O2-O3 diskolysis.