BACKGROUND: The main treatment for Celiac Disease (CD) is the gluten-free diet (GFD). However, in some CD patients, iron deficiency anemia can be persistent despite a GFD. AIM: In this study, we aim to evaluate the prevalence of anemia in both adults and children with CD at the diagnosis and during the GFD. METHODS: In this cross-sectional study including both adults and children with CD, the demographic characteristics and hemoglobin, iron, folate and vitamin B12 levels were retrospectively retrieved from patients' medical records at the time of diagnosis (T0); after 3-5 years (T1) and after 8-10 years (T2) of GFD. RESULTS: 311 CD patients (184 adults and 127 pediatric patients) were included in the study. No difference was observed in the prevalence of anemia in the overall population after 3-5 years of GFD in both adult and pediatric patients compared to the diagnosis. At 8-10 years, in the adult patient's group, a significant reduction in the prevalence of anemia was observed (24% vs. 17.8% p = 0.043). CONCLUSIONS: Despite the GFD and a very long observational period the diagnosis of anemia persists in 17.8% and 4.4% of adult and pediatric patients, respectively. The diagnostic delay (longer in adult patients) and a more pronounced ultrastructural mucosal injury could play a role in the persistence of anemia despite the GFD.