Treatment of calvarial defects has remained a challenge in reconstruction surgery, especially because of infection at these sites. We produced a bactericidal biomaterial for treating infected bone defects by using calcium phosphate bone cement mixed with antibiotics. We evaluated the usefulness of this material mixed with the antibiotic vancomycin in a cranium-infected rat model. The concentration of vancomycin used was 5.0 wt%, as reported in our previous study. In order to establish the rat model, a cranium defect (diameter, 5 mm) was made that was infected with methicillin-resistant Staphylococcus aureus (MRSA). Thirty-six rats were divided into 6 groups depending on whether an autologous graft or bone cement with or without antibiotic was used for the defect. After 1 and 4 weeks, abscess formation was checked, tissue bacterial counts were determined, and pathological examination was performed. At both 1 and 4 weeks, no MRSA was detected on tissue bacterial culture or pathological examination in groups that received bone cement with antibiotics. In groups that received bone cement without antibiotic, MRSA was detected, and the bone cement had compromised and disintegrated into several slices. In conclusion, bone cement that contains antibiotics appears to be effective not only for reconstruction in cases of cranial defect, but also in terms of preventing infection.