BACKGROUND: Data about the relationship between chest radiographs and sputum bacillary load, with treatment outcomes, in patients with extensively drug-resistant tuberculosis (XDR-TB) from HIV/TB endemic settings are limited. METHODS: Available chest radiographs from 97 South African XDR-TB patients, at the time of diagnosis, were evaluated by two independent readers using a validated scoring system. Chest radiograph findings were correlated with baseline sputum bacillary load (smear-grade and culture time-to-positive in MGIT), and prospectively ascertained clinical outcomes (culture conversion and all-cause mortality). RESULTS: Radiographic bilateral lung disease was present in 75/97 (77%). In the multivariate analysis only a higher total radiographic score (95% CI) was associated with higher likelihood of death [1.16 (1.05-1.28) p=0.003], and failure to culture convert [0.85 (0.74-0.97) p=0.02]. However, when restricting analyses to HIV-infected patients, disease extent, cavitation, and total radiographic scores were not associated with mortality or culture-conversion. Finally, cavitary, disease extent, and total radiographic scores all positively correlated with bacterial load (culture time-to-positive). CONCLUSIONS: In endemic settings, XDR-TB radiological disease extent scores are associated with adverse clinical outcomes, including mortality, in HIV uninfected persons. These data may have implications for clinical and programmatic decision-making and for evaluation of new regimens in clinical trials.