BACKGROUND CONTEXT Cervical total disc replacement, TDR, is increasingly accepted as a surgical treatment option for patients who have failed conservative care of single-level conditions. However, coverage for multilevel disease, which is more common, is usually restricted to fusion surgery. Multilevel conditions are more challenging as some levels have soft disc conditions favoring TDR and other levels have bony stenosis and facet overgrowth favoring fusion (ACDF). The purpose of this study was to compare off-label hybrid TDR/ACDF to multilevel ACDF for multilevel cervical disease. PURPOSE Comparison of off-label hybrid TDR/ACDF to multilevel ACDF for multilevel cervical degenerative conditions. STUDY DESIGN/SETTING Two cohort prospective study. PATIENT SAMPLE Consecutive patients who had cervical hybrid procedure with minimum 5-yr follow-up. Historical prospectively analyzed multilevel ACDF control cohort that could have had hybrid if insurance would have approved. OUTCOME MEASURES Neck and arm pain VAS, Pain Drawing, disability outcomes, self-report of success. METHODS Consecutive Hybrid TDR/ACDF patients, n=83, who had minimum of 5 years follow-up were compared to controls. The Hybrid group had the TDR placed at the level were the primary condition was (soft) disc-related whereas the ACDF was performed at the level(s) where the primary condition was bony stenosis or spondylotic. The control group was evaluated prospectively and those with central stenosis were eliminated as they were not satisfactory hybrid candidates. Secondary surgeries were also analyzed for all cohorts. Within the hybrid cohort, 2/3 had a hybrid construct at their index surgery and 1/3 had TDR adjacent to a prior ACDF. RESULTS There were no demographical differences between the two cohorts. Both hybrid TDR/ACDF and multilevel ACDF groups had similar preoperative pain and disability and, within both cohorts, had significantly improved outcomes after surgery. Between groups, there were no differences in outcomes for any of the measures over the 5+ year follow-up. Narcotic medication usage decreased; from 75% preop in the hybrid group to 19% at 3-5 years postop. Secondary surgeries found that over 5 years, adjacent level surgery was in 6 (7%) and 11(14%) patients in the Hybrid and the multilevel ACDF groups respectively. Pseudarthrosis repair was 6% vs 7% in the hybrid and multilevel ACDF cohorts respectively. The study appears valid in that our single-level TDR vs ACDF results were similar to that reported in multiple prior studies and found slightly better outcomes for single-level cervical TDR relative to ACDF. CONCLUSIONS Hybrid TDR/ACDF, used off-label, gives comparable outcomes to multilevel ACDF patients at medium-term follow-up. Secondary surgeries due to adjacent segment disease were half as frequent in the Hybrid cohort. A hybrid procedure is a viable treatment option for patients with multilevel cervical disease. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.