OBJECTIVE To review our results using free-tissue transfer to reconstruct midfacial and cranio-orbito-facial defects. METHODS Case series. METHODS The University of Iowa Hospitals and Clinics, Iowa City. METHODS Fourteen of 21 patients had defects that resulted from ablative oncologic surgery; six had severe mid-facial trauma; and one had Romberg's disease. METHODS Four latissimus dorsi, 11 rectus abdominis, three scapula, and four forearm free-tissue transfer flaps were used. METHODS Adequate flap separation of vital structures (intracranial contents and carotid artery) from the sinonasal or oropharyngeal cavities; restoration of palatal competence, oral diet, and speech intelligibility; maxillary dental rehabilitation; aesthetic results; complications; and the patient's return to social activities outside the home after surgery. RESULTS The intracranial contents (six cases) or carotid artery (four cases) were protected from sinonasal or oropharyngeal contamination by the reconstructive flap in all cases in which this was required. Functional closure of the palate with the flap or a prosthesis was possible in 12 of the 13 patients with a palatal defect; seven of these 13 patients have had full maxillary dental rehabilitation. Twenty patients take an oral diet. Sixteen patients have normal or easily understood speech. Fourteen patients engage in social activities outside the home, and eight have returned to full-time employment. No vascular flap failures occurred in this series. CONCLUSIONS The use of free-tissue transfer flaps is a safe and effective technique for repairing large midfacial and cranio-orbito-facial defects resulting from ablative oncologic surgery or trauma.