The purpose of this study was to investigate the effect of calcium sulfate impregnated with vancomycin combined with internal fixation in the treatment of open fractures of long bones. Between October 2007 and January 2008, twenty-eight patients (24 men, 4 women) who sustained open fractures of long bones were enrolled. Mean patient age was 34.5 years (range, 19-57 years). According to the classification system developed by Gustilo and Anderson, there were 15 type II open fractures, 11 type IIIa open fractures, and 2 type IIIc open fractures. All the patients were treated with vancomycin-loaded calcium sulphate and internal fixation. Clinical signs of wound infection were recorded. Postoperative radiographs were used to evaluate the bone healing and absorption process.Twenty-six of 28 patients were followed-up successfully, with an average follow-up of 10.5 months (range, 6-16 months). No infection was present in the 26 patients. Exudation from the incision or the drain incision was observed in 2 patients. Bacteria culture was negative and the wound healed with dressing change within 15 days. Bone union was observed in 23 patients, with a mean bone union time of 5.8 months (range, 4-9 months). All the calcium sulfate pellets had completely resorbed in an average of 1.4 months (range, 1-2 months). Our study showed that the combination of internal fixation and calcium sulfate impregnated with vancomycin could decrease the incidence of deep infection without impairment to the bone healing process in the treatment of open fractures of long bones.