This article reports on a multicenter evaluation of a novel, sterile, antigen-inactivated, mineralized block allograft in humans during a 3-year developmental period. Consecutive partially edentulous patients (n = 73) with severe localized ridge defects (n = 82) were treated with the material. After 4 to 6 months of healing, tapered screw implants were placed in the grafted bone and subsequently restored. Patients were monitored 25 to 36 months after prosthetic restoration. A biopsy was taken of one patient and submitted for histomorphometric analysis. Block allograft survival was 93% at 12 months, and resorption ranged from none (69%) to slight (0 to 2 mm) (31%) for all surviving allografts. Seven block allografts failed and were removed because of improper contouring, prosthesis impingement, and/or infection. The sites were successfully re-treated and restored with dental implants. Soft tissue dehiscence was successfully treated in seven other sites. Implant survival was 99%. One implant failed without allograft failure. It was replaced with a larger-diameter implant, treated with guided bone regeneration, and subsequently restored. Histomorphometric analysis showed rapid incorporation of the allograft at 6 months without inflammation or necrosis. The block allografts were more technique-sensitive than autografts, which necessitated meticulous surgical technique and follow-up. Short-term results for the block allografts indicated a high degree of predictability, but long-term follow-up is needed.