Animal models of osteomyelitis traditionally have been characterized by inherent weaknesses related to animal size, differences in clinical findings compared with humans, aggressive behavior, high complication rate, and high cost. In this experiment, a model of tibial osteomyelitis was established in 28 goats with a very low complication rate and a consistent clinical, radiographic, and histologic disease course. The infecting Staphylococcus aureus organism was isolated in all but five of 28 animals (82%), in which there was no growth of bacteria at 24 and 72 hours. All five of these specimens had histologic evidence of osteomyelitis. Twenty-seven of the 28 animals (96%) had radiographic and histologic evidence of osteomyelitis. Clinical progression of the disease was observed by draining wounds, a postoperative limp that subsided in all goats, and varied periods of anorexia despite an average increase in body weight. There were no complications or mortalities related to the establishment of the animal model. This large animal model will provide a practical method of studying osteomyelitis and comparing treatment protocols.