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Prospective study analyzing midterm clinical results of total lumbar disc replacement (ProDisc II) for different indications.To assess functional outcome after total lumbar disc replacement (TDR) treated for varying indications.Despite its frequent use and increasing popularity, indications and contraindications for TDR have not been defined precisely at this stage and remain a matter of debate, leading to disc replacement procedures in a variety of pathologies that have not yet been evaluated and compared separately.Patients meeting inclusion criteria were evaluated prospectively according to Visual Analogue Scale (VAS), Oswestry Questionnaire, SF-36, and numerous clinical parameters. Indications included degenerative disc disease (DDD), DDD with accompanying soft disc herniation (nucleus pulposus prolapse, NPP), osteochondrosis following previous discectomy, and DDD with presence of Modic changes. Postoperative improvement was recorded and analyzed for influence of preoperative diagnosis.Overall, 92 patients from four groups with a mean follow-up of 34.2 months (minimum, 24 months) achieved significant and maintained improvement from preoperative levels (P < 0001). Patients with DDD + NPP achieved results significantly better than patients from the other groups (P < 0.05). Presence of Modic changes or previous discectomy did not influence outcome negatively. Improvement was achieved for both monosegmental and bisegmental disc replacements (P < 0.05), nevertheless with significantly inferior results for bisegmental interventions at 12- and 24-month follow-up and considerably higher complication rate. While older patients were still highly satisfied with postoperative outcome, better functional outcome was observed in younger patients.Present data suggest beneficial clinical results of TDR for treatment of DDD in a highly selected group of patients. Better functional outcome was obtained in younger patients under 40 years of age and patients with degenerative disc disease in association with disc herniation. Multilevel disc replacement had significantly higher complication rate and inferior outcome. Results are significantly dependent on preoperative diagnosis and patient selection, number of replaced segments, and age of the patient at the time of operation. Because of significantly varying outcomes, indications for disc replacement must be defined precisely.