BACKGROUND: Deterioration of quality of life in the long term has been suggested for celiac disease patients on a gluten-free diet. AIMS: To determine long-term quality of life of celiac disease patients and to assess the benefits of gluten-free diet compliance. PATIENTS: We prospectively evaluated 53 newly diagnosed adult celiac disease patients. METHODS: The Short Form 36 Health Survey, the Gastrointestinal Symptoms Rating Scale and the Beck Depression Inventory were employed at the time of diagnosis, 1 year, and beyond 4 years (median: 53 months) on treatment. RESULTS: At 1 year, a significant improvement from baseline in quality of life indicators was observed (p<0.001 to p<0.0001) with comparable scores to healthy subjects. At 4 years, the Short Form 36 Health Survey scores (p<0.002 to p<0.0002) and Beck Depression Inventory score (p<0.002) show significant deterioration compare with 1 year. Most scores remained significantly better than those at diagnosis (p<0.03 to p<0.0005). No changes were detected in the Gastrointestinal Symptoms Rating Scale scores. The long-term impairment of quality of life was attributable to the deterioration of most dimensions in patients who were not strictly compliant with the gluten-free diet (p<0.05 to p<0.001). CONCLUSIONS: Long-term deterioration of quality of life outcomes after the first year of gluten-free diet was associated with the lack of strict compliance with the diet.