Background context A relatively high pseudarthrosis rate is associated with multilevel anterior cervical discectomy and fusion (ACDF). Anterior plate fixation increases fusion rate in multilevel ACDF. A debate still exists between the effectiveness of allograft versus autograft in plated multilevel ACDF. Purpose To determine the efficacy of allograft versus autograft in fusion rate and clinical outcome in patients undergoing two- and three-level ACDFs with rigid anterior plate fixation. Study design A retrospective radiographic and clinical review to assess fusion, risk factors and clinical outcome of 80 consecutive patients who underwent ACDF with rigid anterior plate fixation involving two and three levels with either allograft or autograft. Patient sample There were 45 patients (56%) who had autogenous iliac crest tricortical grafts and 35 patients (44%) who received tricortical allograft with an average age of 49 years who were treated by multilevel ACDF with rigid anterior plate fixation at a single institution. Thirty-three Peak polyaxial (Depuy-Acromed, Rayham, MA), 26 Orion (Sofamor-Danek, Memphis, TN), 16 Atlantis (Sofamor-Danek, Memphis, TN) and 5 Synthes (Paoli, PA) anterior cervical plating systems were used. All patients underwent ACDF (61 two-level, 19 three-level) by a Smith Robinson technique. All patients had burring of the end plates, 2-mm distraction of the motion segment and graft countersunk 2 mm from the anterior vertebral border. Anterior cervical plate with unicortical screw purchase was used in all cases. Segmental screw fixation was performed in 46 patients. Soft collars were worn postoperatively for 3 to 4 weeks. Outcome measures Follow-up lateral neutral, flexion and extension radiographs were used to assess fusion. The radiographs were reviewed by an independent blinded observer in assessing fusion grades between autograft versus allograft. Clinical outcomes were rated excellent, good, fair and poor based on Odom's criteria. Methods Fusion rate and postoperative clinical outcome were assessed in 80 patients who underwent two- or three-level ACDF with rigid anterior plate fixation. Additional risk factors were also analyzed. Results Radiographic fusion was assessed in all patients (mean, 16 months). Seventy-eight patients (97.5%) achieved solid arthrodesis. Pseudarthrosis occurred in two patients who had allograft for two-level and three-level fusions. Nonsegmental screws were used in the two-level nonunion case. Postoperative dysphagia developed in one two-level nonunion patient, and revision surgery was performed in the other nonunion three-level patient. Twenty-three patients were smokers, and 26 patients had work-related injuries. Clinical outcome (mean, 20 months) was excellent in 23, good in 48 and fair in 9 patients. No statistical significance was noted between demographics, history of tobacco use, graft-type, end plate preparation technique, intermediate segmental screws, plate-type, clinical outcome of fused and nonfused patients and presence of work-related injuries (p > .05). Conclusions A high fusion rate of 97.5% was obtained for multilevel ACDF with rigid plating with either autograft or allograft. In this study, nonunion occurred in patients with allograft but this difference was not statistically significant. Fusion was obtained in 97.8% of patients with segmental screw fixation and 97.1% with nonsegmental screw fixation. Nonsegmental screw fixation may contribute to less than adequate stability and contribute to a higher rate of nonunion, but such effects could not be discerned from this study. Excellent and good clinical outcome was noted in 88.8% of the patients. Proper patient selection and meticulous operative technique is essential to obtain high fusion rates and optimal clinical outcome, which is more important than graft type.