The authors conducted a prospective study of 132 patients requiring interbody fusion without instrumentation following anterior cervical discectomy to compare the efficacy of tricortical iliac crest allograft versus autograft fusion substrates. The objectives of the study were to assess the potential differences in interspace collapse, angulation, maintenance of cervical alignment and lordosis, and clinical and radiographic fusion success rates between the two fusion substrates. The impact of habitual cigarette smoking on fusion rates was also examined. Autograft tricortical iliac crest bone was found to be superior to allograft bone as an interbody fusion substrate after both single- and multiple-level anterior cervical decompression procedures with respect to maintenance of cervical interspace height, interspace angulation, and radiographic and clinical fusion success rates. Cigarette consumption had a significant adverse effect on successful anterior cervical interbody fusion for both autograft and allograft substrate, an effect that was most pronounced among smokers treated with allograft bone (p = 0.004).