Reconstruction of large anterior vertebral column defects is indicated in a number of pathological conditions including tumor, infection, trauma and post-traumatic deformity. Several substitutes and techniques are available for the functional restoration of the vertebral column. Vascularized bone transfers, autografts, allografts or xenografts have been used, as well as metal or ceramic implants. All of these bear potential advantages and drawbacks in terms of associated morbidity of graft harvesting, disease transmission, mechanical failure, implant incorporation and overall long-term clinical outcome. In the present paper we report our experience with the use of freeze-dried, gamma-irradiated, cortical allograft for the reconstruction of large, anterior segmental defects of the spine, involving at least one vertebral body with its two adjacent discs. Cortical allografts were used in 67 cases operated for a variety of conditions. No case of disease transmission, infection or long-term mechanical graft failure occurred in our entire series, with a mean follow-up of 31 months. Fusion and mechanical stability was reliably obtained. Specific advantages include the absence of donor site morbidity, the possibilities for exact trimming to the size of the defect, superior mechanical strength as compared to available autograft, and reliable fusion with the host bone with partial bone remodeling, preventing fatigue failure. We conclude that freeze-dried, irradiated cortical allografts are safe and effective for anterior reconstruction of the spine.