The effect on quality of life (QOL) of laryngectomy and organ preservation protocols is important in decision making. The aim of this cross-sectional study was to evaluate QOL outcomes of patients with advanced laryngeal tumors who were treated with laryngectomy or organ preservation protocols in Latin America. A total of 35 patients from three oncology units were enrolled. Patients with stage III/IV laryngeal cancer who were treated using organ preservation protocols or laryngectomy were assessed with the University of Washington QOL Questionnaire. The most important domains that affected QOL for both groups were speech and activity. In the laryngectomy group, the next most important domains were appearance, taste, pain, and recreation, whereas in the organ preservation group, they were saliva, recreation, mood, and swallowing. There were no statistically or clinically significant differences in the global score or the 7 days of QOL assessments before patients were interviewed. Global QOL assessments were similar when comparing laryngectomy and organ preservation protocols.