Background: Low-intensity transcutaneous ultrasound can accelerate and augment the fracture-healing process. The aim of this study was to investigate the effect of transosseous application of low-intensity ultrasound on fracture-healing in an animal model. Methods: A midshaft osteotomy of the left tibia was performed in forty sheep. An external fixator was used to stabilize the osteotomy site. A thin stainless-steel pin was inserted into the bone, 1.0 cm proximal to the osteotomy site. Ultrasound was transmitted through the free end of this pin, with a PZT-4D transducer. In twenty animals, the treated limb received a 200-musec burst of 1-MHz sine waves repeated at 1 kHz with an average intensity of 30 mW/cm(2) for twenty minutes daily. Twenty other animals underwent the same surgery but did not receive the ultrasound (controls). Animals were killed at seventy-five and 120 days postoperatively. Radiographic evaluation was performed every fifteen days. Mechanical testing and quantitative computed tomography were performed after death. Results: Fractures treated with ultrasound healed significantly more rapidly, as assessed radiographically, than did the controls (seventy-nine compared with 103 days, p = 0.027). On day 75, the mean cortical bone mineral density (and standard deviation) was 781 +/- 52 mg/mL in the treated limbs compared with 543 44 mg/mL in the control group (p = 0.014), and the average ultimate strength (as assessed with a lateral bending test) was 1928 +/- 167 N in the treated limbs compared with 1493 112 N in the control group (p = 0.012). No significant differences were noted on day 120. Conclusions: This study demonstrated that low-intensity transosseous ultrasound can significantly accelerate the fracture-healing process, increase the cortical bone mineral density, and improve lateral bending strength of the healing fracture in a sheep osteotomy model. Clinical Relevance: Transosseous application of low-intensity ultrasound at close proximity to the fracture site may enhance the mechanical properties of the fracture callus and reduce the time to fracture-healing. However, further investigation is needed to establish the safety and efficacy of the technique.