Antibiotic impregnated beads are being used increasingly in the initial treatment of open fracture wounds, producing high antibiotic levels localy, over the first few days. Pellets were prepared to assess the release of the following antibiotics: benzylpenicillin, flucloxacilin, amoxycillin, amoxycillin-clavulanate (Co-Amoxiclav), ciprofloxacin, imipenem, or gentamicin; the carrier material was either polymethylmethacrylate (PMMA) or plaster of Paris (PoP). Elution of antibiotic over 72 hours from the pellets in vitro was determined using an agar-diffusion microbiologic assay. The initial rapid release of antibiotic lasted 12–24 hours, with release from PoP pellets at least four-fold greater than that from corresponding PMMA pellets. A second phase consisted of a sustained but gradually diminishing elution. The release of antibiotics from PoP pellets compared favorably with that from the PMMA beads currently used. We conclude that PoP pellets may be particularly suitable for short-term applications such as infection prophylaxis in open fractures.