Hydroxyapatite cement is a relatively new biomaterial that has found widespread use in craniomaxillofacial surgery. Despite its common usage, complication rates as high as 32% have been reported. When failed implants are removed, implant fracture has been cited as a potential cause of failure. The purpose of this study was to evaluate resistance to fracture among 4 commercially available hydroxyapatite cement formulations. The materials tested included Norian Craniofacial Repair System (carbonated apatite cement) (AO North America, Devon, PA), Norian CRS Fast Set Putty (carbonated apatite cement) (AO North America), BoneSource (hydroxyapatite cement) (Stryker Leibinger, Portage, MI), and Mimix (hydroxyapatite cement) (Walter Lorenz Surgical, Inc, Jacksonville, FL). To ensure consistency, all materials were embedded in acrylic wells. Each material was placed into a well 2.54 cm in diameter and 0.953 cm in thickness. The materials were prepared per manufacturer specifications. All materials were incubated at 37.0 degrees C, in 6% CO2, 100% humidity for 36 hours. Using the Bionix MTS Test System, a 12-mm-diameter probe applied incremental force to the center of the disk at a rate of 0.1 mm per second. The transmitted force was measured using a Bionix MTS Axial-Torsional Load Transducer for each disk. The force which resulted in fracture was recorded for each material. Ten disks of each material were processed by this method, for a total of 40 disks. The significance of resistance to fracture for the 4 compounds was analyzed using 1-way analysis of variance with post hoc Scheffe method. Mean fracture force with related P values was plotted for direct comparison of group outcomes. Material type contributed significantly to variance in fracture force for the biomaterials studied. Norian CRS required the greatest mean fracture force (1385 N, SD+/-292 N), followed by Norian CRS Fast Set Putty (1143 N, SD+/-193 N). Mimix required a mean fracture force of 740 N, SD+/-79 N. BoneSource required a mean fracture force of 558 N, SD+/-150 N. Mimix and BoneSource required significantly less force for fracture when compared with Norian CRS and Fast Set Putty (P<0.01). Comparisons of fracture load resistance between 4 commonly used bone substitute materials have not been previously reported. Increasing biomaterial strength may reduce complications resulting from reinjury to cranioplasty sites. In this model, Norian CRS and Norian CRS Fast Set Putty demonstrated a significantly greater resistance to fracture when compared with BoneSource and Mimix.