We investigated the use of an ofloxacin-impregnated bioabsorbable composite for the prevention of acute Staphylococcus aureus osteomyelitis. New Zealand White rabbits were anesthetized, the femur was exposed, and a cortical hole was drilled. Animals were randomly given drug-free composites or ofloxacin-impregnated composites; the composites were placed at the site of injury, and the incision was closed. One hour later, all animals were intravenously inoculated with 5 × 10⁴ CFU of S. aureus and observed for 28 days. Bone culture data revealed that S. aureus was isolated from 3 of 12 rabbits in the ofloxacin composite group and 9 of 11 animals in the control group (P = 0.02). Radiographic evaluation revealed that the drug-free group had a significantly (P = 0.01) greater degree of radiographic evidence of infection than the group given ofloxacin composites. Although a limited number of histologic samples were available, these data also paralleled the radiographic and culture data. This study demonstrates the effectiveness of the implantable ofloxacin bioabsorbable composites to prevent the development of acute osteomyelitis.