Data on factors governing long-term adherence to a gluten-free diet (GFD) in celiac disease (CD) are scarce. We aimed to determine trends and clinical predictors of long-term GFD adherence in adult CD.Initial and long-term (>3 years) GFD adherence, clinical characteristics at baseline and follow-up were collected retrospectively from celiac patients followed-up over 20 years (2000-2020). Predictors of long-term GFD adherence at diagnosis, and follow-up were evaluated by multivariate logistic regression.248 patients (37±12 years, 186F, median time on a GFD 90 months) were included. Twenty-five (10.1%) had only short-term follow-up (<3 years) while 223 (89.9%) had initial and long-term dietary assessment. 187/223 (83.9%) patients were initially adherent and 36/223 (16.1%) were not. 17/36 (47.2%) patients initially not adherent become adherent, while only 4/187 (2.1%) initially adherent patients became not adherent. In the long-term 200/223 (89.7%) were adherent and 21/223 (9.4%) patients were not. Adherence improved more frequently than worsened (OR 39.5, 95%CI 11.4-178.5, p<0.01). Classical symptoms (diarrhea,weight loss) at diagnosis of CD predicted stricter long-term GFD adherence (OR 3.27, 95%CI 1.21-8.81; p=0.02), while anemia (OR 0.31, 95%CI 0.12-0.82; p=0.02) and dermatitis herpetiformis (OR 0.23, 95%CI 0.06-0.91; p=0.04) predicted poorer long-term adherence. At follow-up, initial GFD adherence (OR 42.70, 95%CI 10.70-171.00; p=0.04) was the major determinant of long-term GFD adherence.GFD adherence changes over time in <10% of patients, generally improving when it does. Major determinants of long-term GFD adherence are classical symptoms at diagnosis and initial adherence to a GFD. Patients with anemia or dermatitis herpetiformis at diagnosis require stricter dietetic input.