This follow-up study compared 2-level total disc replacement (TDR) with a Mobi-C cervical artificial disc to anterior cervical discectomy and fusion (ACDF) over a period of 48 months, to determine if benefits were sustained since the 24 month prior study. 330 patients with degenerative disc disease received one of the treatments upon randomization in a 2:1 ratio. While both groups improved visibly in clinical outcome measures and safety, patients who received total disc replacement had statistically more favorable scores based on the Neck Disability Index, 12-Item Short Form Health Survey Physical Component Summary, patient satisfaction, and overall success. Additionally, total disc replacement offered lower rates of subsequent surgery and adjacent-segment degeneration.