There are few data from tuberculosis (TB) endemic settings of the performance and outcome predictors of the QuantiFERON-TB Gold in Tube assay (QFT) in children with suspected TB. A prospective cross-sectional study was conducted in Papua New Guinea children with suspected TB evaluated at Port Moresby General Hospital (Port Moresby, Papua New Guinea). Two hundred sixteen children were enrolled including 106 probable TB, 87 possible TB and 23 without TB. Concordance between QFT and tuberculin skin test results was 86% (P < 0.001, κ = 0.70). QFT was significantly more likely to be positive than tuberculin skin test, overall and within the probable or possible TB categories, with no difference in prevalence of positivity between these 2 categories. The role of QFT in supporting the clinical diagnosis of TB in endemic settings, where resources are limited, remains uncertain especially as cost and technical requirements remain considerable.