INTRODUCTION: Celiac disease (CD) affects health-related quality of life (HRQOL) of patients suffering it. The exclusion of gluten from the diet (GFD) improves HRQOL, but involves difficulties in following the diet that could adversely affect HRQOL. OBJECTIVE: To determine the effect of adherence to the diet on HRQOL of adult CD patients. METHODS: A prospective, cross-sectional, multicenter study of CD patients treated with a GFD for longer than 1 year. Adherence to the GFD was measured using the Morisky scale, and health status using the specific CD-QOL questionnaire and the generic EuroQol-5D questionnaire. RESULTS: 366 patients from 7 hospitals were included: 71.5% of patients reported a perfect treatment adherence, 23.5% unintentional poor adherence and 5% intentional poor adherence. Good adherence to a GFD was related to a higher mean score onthe CD-QOL (75 vs. 68, respectively, p < 0.05) and EuroQol-5D (0.9 vs. 0.8, respectively, p < 0.05). Ease of adherence to a GFD was also related to a better HRQOL (total CD-QOL score of 82 vs. 67 in patients who consider the GFD difficult to follow, p < 0.05). Good symptom control was also related to a better HRQOL (total CD-QOL score of 78 vs. 67 in asymptomatic vs. symptomatic patients, p < 0.01). The worse scored dimension of CD-QOL was related to "inadequate treatment". CONCLUSIONS: In CD, good adherence to a GFD and adequate symptom control result in improved HRQOL. Many patients consider that the lack of therapeutic alternatives to diet worsens their quality of life.