Background: The epidemiology and management of nontuberculous mycobacterial (NTM) infection in Australian children is unknown.Methods: From July 2004 to June 2007, clinicians identified children with NTM infection as part of a nationwide active surveillance network. Following notification, detailed data were collected.Results: From 192 reports, data were received on 153 cases (response rate: 79.7%). Of these, 102 met inclusion criteria. The median age was 2.9 years. Predisposing conditions were infrequent and included chronic respiratory disease (n = 12) and immunosuppression (n = 6). Lymphadenitis was the most frequent presentation (n = 68) with pulmonary and disseminated disease infrequent (n = 14 and 3, respectively). NTM was isolated in 68 cases with Mycobacterium avium-intracellulare complex most frequently isolated (33/68; 48.5%). Surgery was performed in 78 cases and 42 children were treated with antimycobacterial therapy. Twenty-five subjects received surgery and antimycobacterial therapy. Follow-up data were available for 77 children with recurrence observed in 18 cases. Complete excision was associated with a higher rate of treatment success when compared with all other therapies (OR: 9.48 [95% CI: 2.00–44.97], P = 0.001). Mycobacterium lentiflavum infection accounted for 4.4% of culture confirmed cases and had a lower rate of treatment success than other species (0% vs. 78.2%; P = 0.016).Conclusions: The incidence of NTM infection in Australian children is 0.84 of 100,000 (95% CI: 0.68–1.02). Infection occurs most often in young children without predisposing conditions. Despite therapy, there was recurrence in 23.4% of cases.