Introduction: Radiation therapy of the oral and maxillo-facial region increases the risk of an infected osteoradionecrosis (IORN) which is a severe complication. Therefore, perioperative antibiotics for the prophylaxis of ORN is a standard in clinical oncology. The combination therapy of ampicillin and sulbactam (Unacid) promises a good therapeutic and prophylactic outcome. Patients: We compared the concentration of Unacid in bone and blood specimens of 22 irradiated patients. All patients were irradiated with 39.6 Gy prior to surgery. The specimens were obtained during the operation 3 weeks after the end of the radiation therapy. Results: The concentration of ampicillin/sulbactam in the blood was 124.9/64.5 μ/ml. The bone specimens showed a concentration of ampicillin/sulbactam of 5.54/1.21 μg/g. The concentration of the antibiotic in the bone was three to four times lower than in non-irradiated patients. Nevertheless, this concentration exceeds the minimum inhibitory concentration for bacteria in the oral cavity such as streptcoccae (MHK ₉₀<0.25 μg/ml) or staphylococcae (MHK ₉₀=0.12-2.0 μg/ml). Conclusions: The results of this study suggest, that Unacid is an effective antibiotic in the prophylaxis of ORN in irradiated patients with head and neck tumors.