Background: Mycobacterium tuberculosis (TB) is a widespread life-threatening infection worldwide. There is an uncertainty in the association between the emergence of autoimmune antibodies and TB. Objectives: We hereby aimed to screen anti-tissue transglutaminase (anti-tTG) IgA in patients with TB in an Iranian population. Methods: This was a cross sectional study conducted on smear positive TB patients admitted to the Respiratory Diseases Management Center of the city of Zabol, Sistan and Baluchestan Province of Iran during 2017 - 2018. Anti-tTG IgA level was determined using an ELISA kit (Pars Azmoun, Iran). Statistical analyses were performed in SPSS 19 software. Results: Overall, 162 patients were evaluated. Females and males constituted 87 (53.7%) and 75 (46.3%) of the patients respectively. The mean age was 51.7 ± 22.3 years (range of 1 - 83). Afghan patients constituted 16 (9.9%) and the remaining were Iranians. The therapy course was successfully completed in 78 (48.1%) patients, and 67 (41.4%) improved following treatments. Overall, 5 patients had active TB with 2 drug-resistant cases. Pulmonary tuberculosis was diagnosed in 127 (78.4%) while 35 (21.6%) had extra-pulmonary disease. The mean titer of anti-tTG IgA was 22.59 ± 107.7 (range of 0.8 - 940). Overall, 19 (11.9%) of the patients showed elevated levels of the antibody. There was no significant association between anti-tTG IgA titer with neither demographic nor clinical variables. Conclusions: Although anti-tTG IgA antibody test was positive in a relatively high ratio of our patients with TB, the clinical implications of this phenomenon were not significant.