The aim of this study was to evaluate the health-related quality of life in patients diagnosed as having celiac disease and to study the factors involved in its impairment of quality of life. We conducted a cross-sectional study in a randomized sample of patients with celiac disease by administering the Celiac Disease Questionnaire distributed by mail. The association between the quality of life and sociodemographic and clinical variables was verified by means of a stepwise multiple regression model. One hundred ninety-one questionnaires were returned (participation rate = 63.66%), and 187 were analyzed. Women comprised 78.61% of the participants, and the median age was 36 years, 10 months. The mean summary total score in the Celiac Disease Questionnaire was 154.53 (possible range 1-196; higher scores equate with higher quality of life), and the score was lower in the subscale of emotion. Women scored significantly lower than men. Participants with the symptomatic disease scored significantly lower than the nearly asymptomatic patients in the total score and in all the subscales. Symptomatic patients need interventions for improving their quality of life, in particular psychological support.