This study evaluates a novel adhesive fixation technique to affix cortical bone fragments to osteosynthesis plates using common PMMA cement. This technique utilizes a new amphiphilic bone bonding agent adhering with both hydrophilic bone and hydrophobic PMMA cement. After in vitro biomechanical testing of the bonding strength with explanted bovine and rabbit calvarian bone samples, osteosynthesis plates with screw holes of 1.3 and 1.5 mm were placed on the cranial bone of New Zealand white rabbits and the bond strength of these plates was determined through tension tests. In vitro bond strengths of 19.8–26.5 MPa were obtained. Control samples, prepared without a bone bonding agent, exhibited bone bonding strengths <0.2 MPa. In vivo respective bond strengths at the cranium of the white rabbits were 2.5–4.1 MPa 2 weeks post surgery and 1.9–2.5 MPa 12 weeks after implantation. This new innovative fixation method can be envisioned for cases in which conventional fixation techniques of screws and plates are insufficient or not possible due to the bone or trauma conditions. The observed bonding strengths support implementing this technique in nonload bearing regions, such as the central midface or frontal sinus, facilitating immobilization until bone reunion is complete. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.