Study design: An animal model of anterior lumbar arthrodesis was designed to investigate whether a calcium phosphate cement (CPC) mixed with autologous whole blood might favourably compete with autograft for enhanced spine fusion. Objective: The objective of this study was to use a large animal model to investigate a new approach for spine fusion which consists in the injection of a highly resorbable CPC / blood composite to fill the interbody fusion cage, once placed in the intervertebral space. Summary of background data: Spinal fusion via intervertebral arthrodesis is a common surgical procedure for which the gold standard consists in filling the internal hollow part of the cage with bone autograft. However, this approach suffers from some drawbacks, including a second surgical site which requires additional time spent in the surgical room, and the occurrence of additional new pain on the bone harvesting site along with risks of long-term morbidity. Methods: An animal model of anterior lumbar arthrodesis involved 14 sheep that received a fusion cage in two non-adjacent lumbar levels. For one-half of the animals, the cages were filled after impaction by injection of a CPC/blood composite in one level and the blood-free CPC reference in the other. For the other seven animals, the CPC/blood composite was compared to bone autograft. Results: SEM and histological examination of the explants gave evidence of a good osteointegration for the three types of implanted materials. For the first group, no spine fusion was observed for the blood-free CPC reference while a highly successful spine fusion (6/7 cages) was present for the CPC/blood composite, three months after surgery. For the second group, successful arthrodesis was observed for 57% (4/7) of cages filled with iliac autograft, while the fusion rate was 71% (5/7) in the case of cages filled with the CPC/blood composite. Conclusion: This study reports that the observed fusion rate when filling the cage with a calcium phosphate cement mixed with autologous whole blood was at least as good as results obtained with autograft. Once placed in the intervertebral space, the cage was easily and homogeneously filled with the CPC/blood composite, and this new strategy might thus offer a less invasive option for intervertebral spine fusion.