62 patients with bi-segmental degenerative disc disease at L4-S1 were randomized to receive either hybrid anterior lumbar interbody fusion (ALIF) at L5/S1 with total disc replacement (TDR) at L4/5 or conventional 2-level circumferential fusion with transforaminal lumbar interbody fusion (TLIF) for the purpose of comparing pain and radiographic parameters throughout a 37-month follow-up period. Results demonstrated that patients in the Hybrid group had significantly reduced pain scores when compared to the Fusion group at both the 1-week and 37-month follow-up points. Additionally, significant increases in segmental lordosis were mainly observed at L4-S1 in the hybrid group (instrumented levels only) compared to L1/-S1 in the Fusion group (instrumented and uninstrumented levels).