OBJECTIVE : To describe the demographic and clinical characteristics of children and adolescents diagnosed with resistance to any anti-tuberculosis drug (drug-resistant tuberculosis; DR-TB) in South Africa. DESIGN : We retrospectively reviewed medical records of all children (<13 years) and adolescents (13 to <18 years) with DR-TB at specialty hospitals in four South African provinces from 2005 to 2010. RESULTS : During the review period, 774 children and adolescents (median age 11.3 years) were diagnosed with DR-TB at selected facilities. A high proportion of patients had a history of previous TB treatment (285/631; 45.2%), human immunodeficiency virus (HIV) infection (375/685; 54.7%), contact with a TB case (347/454; 76.4%), and smear-positive (443/729; 60.8%), cavitary (253/680, 38.7%) disease. Eighty-two per cent of patients with HIV infection received antiretroviral therapy. Of 626 patients diagnosed with multidrug-resistant TB (MDR-TB), 561 (89.6%) received a regimen consistent with national guidelines; the median length of treatment was 22 months (IQR 16-25). Among 400 patients with any DR-TB and a known outcome, 20.3% died during treatment. CONCLUSION : Pediatric DR-TB in these provinces is characterized by complex clinical features at diagnosis, with one in five children dying during treatment. History of previous treatment and contact with a TB patient indicate opportunities for earlier diagnosis and treatment to improve outcomes.