The aim of this study was to investigate the role of dispositional optimism (DO) as a predictor of health-related quality of life (HRQL) in a sample of upper aerodigestive tract cancer (UADT) patients. A prospective observational study design was used with a cohort of patients from one centre. DO was evaluated using a French version of the Life Orientation Test (the FLOT) translated and validated for this study. HRQL was evaluated using the EORTC QLQ-C30 prior to and 3 months following treatment. The association between FLOT ratings and HRQL was evaluated using linear multiple regression analysis and a two-way ANOVA with repeated measures. Baseline data were gathered on 101 subjects and follow-up data on 88 of these. The sample was dichotomized around the median FLOT score creating 'optimist' and 'pessimist' groups. Before treatment, optimists reported better role, cognitive and emotional function, less pain and fatigue and a better global rating of HRQL than did pessimists. Following treatment, optimists reported better role and cognitive functioning, less pain and better global HRQL than did pessimists. Pessimists reported a greater deterioration in the role domain following treatment than did optimists. At no point did pessimists rate HRQL better than optimists. The results suggest that optimism is associated with better HRQL in French UADT cancer patients.