BACKGROUND.: We conducted this prospective longitudinal multicenter study to evaluate the health-related quality of life (HRQL) of patients with oral carcinoma at diagnosis, and after 1 and 5 years in relation to tumour location and treatment modality. METHODS.: One hundred twenty-two patients (mean age, 61; 62% males) with oral carcinoma were evaluated with standardized HRQL questionnaires, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core30 (EORTC QLQ-C30) and the EORTC Head and Neck Cancer Module (EORTC QLQ-H&N35). RESULTS.: Problems with teeth, dry mouth, and sticky saliva got worse between diagnosis and 5 years after diagnosis. Problems with dry mouth remained a problem between 1 and 5 years after diagnosis, except for the patients treated with surgery only. This group had fewer problems over time compared with patients receiving other treatment regimes. Survivors reported better HRQL than the nonsurvivors at diagnosis and at the 1-year follow-up. HRQL at diagnosis was associated with survival. CONCLUSIONS.: HRQL at diagnosis for patients with oral carcinoma seems to be an important factor for the prognosis of both HRQL over time and survival. Treatment of oral carcinoma often results in long-term side effects such as dry mouth, problems with teeth, and sticky saliva. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2008.