BACKGROUND: Few studies have described the management of multidrug-resistant (MDR) tuberculosis (TB) in children and evidence-based guidance on management is lacking. We describe the presentation, treatment and outcome in children treated for severe and non-severe MDR-TB in Cape Town, South Africa. METHODS: We conducted an observational cohort study of all children (<15 years) treated for MDR-TB if routinely initiated on treatment between January 2009 and December 2010. Treatment was based on local standard of care, based on international guidelines. Data were collected through family interviews and folder review. Standardised definitions were used for diagnosis, severity of disease, adverse events and outcome. RESULTS: Of 149 children started on MDR-TB treatment, the median age was 36 months (IQR 16-66), 32 (22%; of 146 tested) had HIV infection and 59 (40%) had a confirmed diagnosis. Ninety-four (66%) children were treated with an injectable drug and the median total duration of treatment was 13 months (IQR 11-18). Thirty-six (24%) children were cured, 101 (68%) probably cured, 1 (1%) was transferred out, 8 (5%) were lost to follow-up and 3 (2%) died. Children with severe disease were older (54 months (IQR 18-142) vs 31.5 months (IQR 17.5-53.5); p=0.012), more commonly had HIV infection (OR 6.25; 95% CI 2.50 to 15.6; p<0.001) and were more likely to die (p=0.008). DISCUSSION: A confirmed diagnosis of MDR-TB is not possible in all cases but this should not impede the treatment of MDR-TB in children. More than 90% of children with MDR-TB can be successfully treated. Non-severe disease could be successfully treated with reduced treatment duration.