Gluten-free diet (GFD) plays a key role in the treatment of celiac disease (CD), but it is difficult to evaluate the effect of GFD on the improvement of villous architecture using sensitive, non-invasive tests. Aim of this study is to evaluate anti-transglutaminase (tTG) antibodies in the follow-up of CD to detect histologic recovery. We studied 42 consecutive patients with CD. In all the patients anti-tTG antibodies (evaluated by the enzyme linked immunosorbent assay method) and EGDscopy with multiple bioptic samples before GFD and then 6, 12, and 18 months after GFD were evaluated. For comparison, a sorbitol H2-breath test (H2-BT) and anti-endomysium (EMA) antibodies test were carried out concomitantly. Anti-tTG results were positive in 36 of 42 patients before GFD (80.95%), while they were positive in 11 of 34 (32.35%), 1 of 17 (5.88%), and 0 of 6 (0%) of patients with a persistence in histologic lesions 6, 12, and 18 months of GFD respectively, without any correlation with persistence of histologic lesions (P = NS). Also EMA failed to show correlation with improvement of histologic lesions. They were positive in 31 of 42 patients before GFD (73.80%), while they were positive in 18 of 34 (52.94%), 3 of 17 (17.64%), and 0 of 6 (0%) cases 6, 12, and 18 months of GFD respectively (P = NS). Regarding sorbitol H2-BT, it was positive in 40 of 42 (95.24%) patients before GFD, while it was positive in 31 of 34 (91.17%), 13 of 17 (76.47%), and 4 of 6 (50%) of patients with a persistence in histologic lesions 6, 12, and then 18 months after GFD starting (see Fig. 2, infra). So, anti-tTG and EMA were ineffective in assessing the histologic recovery at each follow-up visit (P = NS), while sorbitol H2-BT seems more effective than anti-tTG and EMA in this field (P < 0.0001 sorbitol H2-BT versus anti-tTG and versus EMA at 18 months after gluten withdrawal). Thirty-eight of 42 (90.47%) patients adhered to a strict GFD. Four patients were found to have occasional dietary transgression, and in all we noted a progressive decreasing of anti-tTG after 6 months of GFD and negative anti-tTG after 12 months of GFD, but sorbitol H2-BT persisted being positive during the entire follow-up. Intestinal damage persisted during the follow-up, despite anti-tTG and EMA negativity, and worsened in the presence of dietary lapses. Anti-tTG does not seem effective to assess histologic recovery in the follow-up of celiac patients after they have started GFD due to its poor correlation with histologic damage.