OBJECTIVES: Current pediatric guidelines allow noninvasive diagnosis of celiac disease in selected children. We investigated in a large cohort study whether the severity of villous atrophy at diagnosis is associated with clinical characteristics or long-term health outcomes, thus having a prognostic significance. METHODS: Comprehensive medical data on 906 children with celiac disease were analyzed. Long-term health outcomes of 503 adult patients diagnosed in childhood were moreover assessed with a specific study questionnaire and validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well-Being (PGWB) questionnaires. Patients were classified into 3 groups according to the severity of villous atrophy at diagnosis, and all variables were compared. RESULTS: Altogether 34% of the patients had partial, 40% subtotal, and 26% total villous atrophy. Children with milder lesions were diagnosed more recently (median year 2007 vs 2006 vs 2001, respectively, P < 0.001), more often by screening (30% vs 25% vs 17%, P < 0.001) and they suffered less often from anemia (16% vs 21% vs 32%, P < 0.001) and growth disturbances (22% vs 36% vs 54%, P < 0.001) and had lower transglutaminase-2 antibody levels (median 64 U/L vs 120 U/L vs 120 U/L, P < 0.001). There was no difference in other disease features.Altogether 212 adults diagnosed in childhood completed the questionnaires. Severity of villous atrophy at childhood diagnosis did not predict presence of complications or comorbidities, persistent symptoms, and self-perceived health, quality of life or adherence to a gluten-free diet in adulthood. CONCLUSION: Presence of advanced villous atrophy at diagnosis is associated with more severe clinical characteristics but not with poorer long-term health and treatment outcomes.