The manual Mycobacteria Growth Indicator Tube (MGIT) method was evaluated for performing direct and indirect drug susceptibility testing (DST) of Mycobacterium tuberculosis for isoniazid and rifampin on 101 strongly smear-positive sputum specimens in a Siberian prison hospital. Using the indirect method of proportion (MOP) as the "gold standard," the accuracies of isoniazid and rifampin susceptibility testing by the direct MGIT system were 97.0 and 94.1%, respectively. The accuracy of the indirect MGIT system was 98.0% for both drugs. The turnaround times from specimen processing to reporting of the DST results ranged between 4 and 23 (mean, 9.2) days by the direct MGIT method, 9 and 30 (mean, 15.3) days by the indirect MGIT method, and 26 and 101 (mean, 59.6) days by the indirect MOP. MGIT appears to be a reliable, rapid, and convenient method for performing direct and indirect DSTs in low-resource settings, but further studies are required to refine the direct DST protocol. Cost is the only factor prohibiting widespread implementation of MGIT.