In an effort to augment the available grafting material as well as to increase spinal fusion rates, the utilization of a demineralized bone matrix (DBM) as a graft extender or replacement is common. There are several commercially available DBM substances available for use in spinal surgery, each with different amounts of DBM containing osteoinductive proteins. Each product may have different osteoinductivity potential due to different methods of preparation, storage, and donor specifications. The purpose of this study is to prospectively compare the osteoinductive potential of three different commercially available DBM substances in an athymic rodent spinal fusion model and to discuss the reasons of the variability in osteoinductivity. A posterolateral fusion was performed in 72 mature athymic nude female rats. Three groups of 18 rats were implanted with 1 of 3 DBMs (Osteofil, Grafton, and Dynagraft). A fourth group was implanted with rodent autogenous iliac crest bone graft. The rats were sacrificed at 2, 4, 6, and 8 weeks. A dose of 0.3 cm3 per side (0.6 cm3per animal) was used for each substance. Radiographs were taken at 2 weeks intervals until sacrifice. Fusion was determined by radiographs, manual palpation, and histological analysis. The Osteofil substance had the highest overall fusion rate (14/18), and the highest early 4 weeks fusion rate of (4/5). Grafton produced slightly lower fusion rates of (11/17) overall, and lower early 4 weeks fusion rate of (2/5). There was no statistically significant difference between the rate of fusion after implantation of Osteofil and Grafton. None of the sites implanted with Dynagraft fused at any time point (0/17), and there was a significantly lower fusion rate between the Dynagraft and the other two substances at the six-week-time point and for final fusion rate (P = 0.0001, Fischer’s exact test). None of the autogenous iliac crest animals fused at any time point. Non-decalcified histology confirmed the presence of a pseudarthrosis or the presence of a solid fusion, and the results were highly correlated with the manual testing. Although all products claim to have significant osteoinductive capabilities, this study demonstrates that there are significant differences between some of the tested products.