Background: Single and multilevel lumbar arthroplasty has had excellent results, but the L5-S1 level frequently has pathology that precludes arthroplasty. This study evaluated clinical outcomes and sagittal range of motion (ROM) of operated levels and adjacent motion segments in single- and multiple-level ProDisc-L above a simultaneous L5-S1 fusion (hybrid) after a 2- to 6-year follow-up. Methods: In this prospective cohort study, 46 patients underwent simultaneous lumbar total disc replacement (TDR) at one to three levels and anterior lumbar interbody fusion (ALIF) at L5-S1. Twenty-three patients had L5-S1 ALIF + L4-5 TDR, 19 patients had L5-S1 ALIF + two-level TDR, and 4 patients had L5-S1 ALIF + three-level TDR. Oswestry disability index (ODI) and visual analog scores (VAS) of patient satisfaction (VAS-S) and pain (VAS-P) were recorded. Sagittal motion on pre- and postoperative lumbar radiographs at each operative segment and adjacent segment was acquired. Patients were evaluated preoperatively and at 6 weeks, 3 months, 6 months, and annually for 24 to 72 months postoperatively. Results: For clinical results, there were no differences among the groups for age, gender, body mass index, tobacco use, or worker's compensation status. At 2-6 years postoperation, all patients had significant reductions in ODI and VAS scores. For radiographic results, at the nonsurgical level adjacent to the TDR + ALIF constructs, the mean preoperative ROM was 9.40 +/- 1.80 degrees compared with 10.50 +/- 2.25 degrees postoperatively. The mean preoperative ROM at levels undergoing TDR was 10.4 +/- 2.71 degrees versus 12.6 +/- 2.25 degrees postoperatively. There was no statistically significant difference in ROM at each prosthetic motion segment between patients receiving one-, two-, or three-level TDR. The mean preoperative ROM at the L5-S1 segment to undergo fusion was 2.4 +/- 2.44 degrees, with all patients having a postoperative ROM of 0.00 degrees. Conclusions: Multilevel TDR above an L5-S1 ALIF (hybrid procedure) preserves ROM at the individual TDR levels and does not reduce the fusion rate of the L5-S1 fused level. Most significantly, the nonoperative adjacent level maintains its preoperative ROM at 2-6 years postoperatively.