The current delivery system of antibiotics for the treatment of osteomyelitis uses polymethylmethacrylate (PMMA) beads as a local drug‐release agent. The nonbiodegradable nature of the PMMA, however, necessitates a second operation to remove the beads. This article explores the alternative of using biodegradable polymers as antibiotic beads for a long‐term drug release in vivo. To manufacture an antibiotic bead, lactide‐glycolide copolymers were mixed with vancomycin. The mixture was compressed and sintered at 55 °C to form beads 8 mm in diameter. An in vivo animal model was proposed to characterize the elution rate of antibiotic over a 55‐day period. Biodegradable beads released high concentrations of antibiotic (well above the breakpoint sensitivity concentration) in vivo for the period of time needed to treat bone infection; that is, 4–6 weeks. A bacterial inhibition test was also carried out to determine the relative activity of the released antibiotics. The diameter of the sample inhibition zone ranged from 8 to 18 mm, which is equivalent to 9.1 to 100% of relative activity. In addition, the antibiotic concentration of systemic blood was found to be very low. Antibiotic‐impregnated biodegradable beads may have a potential role in the prevention and management of surgical infections. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 807–813, 2002