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Background The optimal treatment for locally advanced laryngeal cancer remains controversial. The purpose of this trial was to determine if the response to induction chemotherapy could select patients for organ preservation protocols, and improve larynx-preservation rates without compromising overall survival (OS). Methods The cohort comprised 12 patients with T3 disease and 14 with T4. Induction chemotherapy consisted of docetaxel, cisplatin, and 5-fluorouracil (TPF). Response to the first cycle was determined by examination and positron emission tomography (PET)-CT. Responders (>50% tumor reduction) underwent chemoradiation, whereas nonresponders underwent laryngectomy. Results Eighty-three percent of the patients had a response and 17% had stable or progressive disease. At 2 years, the median OS was 80%, the larynx-preservation rate was 83%, and the disease-specific survival rate was 86%. Response to a single TPF cycle was associated with 2-year OS (92% vs 50%; p = .02). The T classification was not predictive of survival. Conclusion Response to a single TPF-based cycle may identify patients with advanced laryngeal cancer who are amenable to organ preservation treatment. © 2016 Wiley Periodicals, Inc. Head Neck, 2016