Introduction: Management of patients after total or subtotal glossectomy presents challenging reconstruction of complex three-dimensional defects. Such defects can have a dramatic effect on respiration, speech, and nutrition, and may significantly impact quality of life. Patients and methods: We present our experience with 39 patients submitted to total or subtotal glossectomy and reconstruction with microsurgical flaps. Functional results are reported in term of swallowing ability, decannulation, and intelligible speech. Oncological outcomes are described in terms of local disease control and overall survival rate. Results: We carried out 24 total glossectomies and 15 subtotal glossectomies. Total glossectomy was associated with a total laryngectomy in eight patients. Reconstruction was performed using Taylor's myocutaneous extended deep inferior epigastric flap in 33 patients, and an anterolateral thigh perforator flap in six patients. A fibula osteocutaneous free flap was raised in two patients with an anterior segmental mandibulectomy. A second free flap was needed in three cases. Wound complications occurred in 17 patients: an orocutaneous fistula in eight patients and a dehiscence of the suture without fistulization in nine patients. Oral feeding was resumed in 33 patients (85%). In nonlaryngectomized patients, decannulation was achieved in 28 (90%) and speech was good or acceptable in 27 (87%). The 5-year adjusted survival for patients treated with total or subtotal glossectomy was 47%. Conclusion: Our results in a relatively large sample of patients who underwent total or subtotal glossectomy followed by reconstruction with microsurgical free flaps support the efficacy of this surgery as treatment for advanced oral and oral pharyngeal cancers. © 2011 Wiley-Liss, Inc. Microsurgery.