Few data are available on tuberculosis (TB) drug resistance patterns in Papua New Guinea (PNG) due to the lack of facilities for mycobacterial culture. Many patients from the Western Province seek care in Queensland health clinics in the Torres Strait. Since 2000, we have treated 161 TB cases from PNG, of whom 40 proved to have multidrug-resistant TB (MDR-TB; two human immunodeficiency virus positive). Drug susceptibility testing (DST) shows high levels of resistance to other drugs in the MDR-TB cases (streptomycin 93%, ethionamide 87%, ethambutol 18%, pyrazinamide 10%). No extensively drug-resistant TB (XDR-TB) has been identified. MDR-TB seems to be highly prevalent in the Western Province of PNG, and unless treatment is guided by DST, the risk of XDR-TB emerging is high.