The microscopic observation drug susceptibility assay (MODS) is a novel and promising test for the early diagnosis of tuberculosis (TB). We evaluated the MODS assay for the early diagnosis of TB in HIV-positive patients presenting to Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases in southern Vietnam.A total of 738 consecutive sputum samples collected from 307 HIV-positive individuals suspected of TB were tested by smear, MODS, and the mycobacteria growth indicator tube method (MGIT). The diagnostic sensitivity and specificity of MODS compared to the microbiological gold standard (either smear or MGIT) were 87 and 93%, respectively. The sensitivities of smear, MODS, and MGIT were 57, 71, and 75%, respectively, against clinical gold standard (MODS versus smear, P < 0.001; MODS versus MGIT, P ؍ 0.03). The clinical gold standard was defined as patients who had a clinical examination and treatment consistent with TB, with or without microbiological confirmation. For the diagnosis of smear-negative patients, the sensitivities of MODS and MGIT were 38 and 45%, respectively (P ؍ 0.08). The median times to detection using MODS and MGIT were 8 and 11 days, respectively, and they were 11 and 17 days, respectively, for smear-negative samples. The original bacterial/fungal contamination rate of MODS was 1.1%, while it was 2.6% for MGIT. The crosscontamination rate of MODS was 4.7%. In conclusion, MODS is a sensitive, specific, and rapid test that is appropriate for the detection of HIV-associated TB; its cost and ease of use make it particularly useful in resource-limited settings.It is estimated by the World Health Organization (WHO) that there were 9.4 million new cases of tuberculosis (TB) in 2008 (24). Of these, 1.4 million (15%) were in HIV-positive patients, and 23% of all HIV-related deaths are estimated to be attributable to TB (23).Vietnam is a high-TB-burden country with steeply rising rates of HIV-TB coinfection (21); 8.1% of newly diagnosed TB patients are now HIV infected (24). These cases are the most urgently in need of diagnosis because they have the highest morbidity and mortality, and yet the diagnosis of TB among HIV-infected individuals is difficult. Screening algorithms based on clinical symptoms alone show high sensitivity but low specificity (5, 25). The microscopy smear method, while simple, specific, and widely available in high-burden settings, has particularly low sensitivity in HIV-infected patients and cannot be used to rule out a diagnosis of TB (13,20). Microbiological confirmation remains desirable and allows investigation of drug susceptibility profiles. Commercial rapid liquid culture techniques have been endorsed by the WHO (27), show higher sensitivity, and are more rapid than traditional solid-mediumbased techniques such as Lowenstein-Jensen culture. However, their high cost and biosafety infrastructure requirements limit their applicability in many high-burden settings. Rapid molecular line-probe assays, also endorsed for use in lowresource settings by the WHO (28), allo...