Drug-induced hepatitis (DIH) is an important issue in tuberculosis (TB) treatment. We intend to assess the incidence, risk factors, and outcome of hepatitis due to anti-TB drugs. The study is carried out at the national TB referral center 2006-2008 including all documented new cases of TB. All patients received standard anti-TB treatment. If DIH occurred, all drugs were discontinued and reinitiated after liver function tests (LFT) normalization in a stepwise way. Of total 761 patients, 99 (13.0%) patients developed DIH during anti-TB treatment. There was no difference in sex, nationality, smoking, or opium use history between the hepatitis group and the control group (P > 0.05). DIH was significantly higher in patients older than 65 years (P = 0.019). The mean duration of DIH from the beginning of treatment was 17.53 +/- 19.42 days (median = 12; 1-125 days). Also, the mean of the time elapsed from DIH till the (LFT) normalization was 10.26 +/- 5.95 (median = 9; 0-32 days). Anorexia, nausea, vomiting, abdominal pain, jaundice, diarrhea, decreased level of consciousness, and fever were significantly higher in patients with DIH. In DIH group, 13 patients (13.4%) died, whereas in the control group, death occurred just in 21 cases (3.2%) (P < 0.001, 95% confidence interval = 2.26-9.70, odds ratio = 4.7). After adjusting with logistic regression, all the anticipated factors retained the statistical significance. Our study indicated that DIH most often occurs during the first 2 weeks of anti-TB treatment. DIH development is associated with old age, certain clinical manifestations, and higher death rates.