Objective -to compare the efficacy of various molecular genetic methods for diagnosing tuberculosis and determining drug susceptibility to rifampicin (RIF). Materials and Methods. We conducted a retrospective study of the sputum analysis results on 1,992 patients with pulmonary tuberculosis treated at Saratov Oblast Clinical Tuberculosis (TB) Dispensary from 2014 through 2018. The following methods were used: real-time polymerase chain reaction (PCR), biological microarrays, automated Xpert® MTB/RIF technology. Statistical processing of the research results was carried out using the Bayes formula based on contingency tables (four-field table) and the χ2 test. When evaluating the significance of differences between relative values, we employed the critical significance level of 0.05. Results. In terms of etiological diagnosis of TB, higher diagnostic sensitivities of the real-time PCR and biological microarray methods (73.9% and 70.3%, correspondingly) were established, as compared with the Xpert® MTB/RIF method (34.2%) (p<0.001). The sensitivity of all methods depended on the massiveness of bacterial excretion and clinical form of TB. Conclusions: The Xpert MTB/RIF method exhibited lower diagnostic sensitivity in verifying the diagnosis of TB, whereas its operational characteristics in terms of determining RIF-resistance were sufficiently high (sensitivity at 89.7%, specificity at 89.1%, and efficacy at 89.4%), which was comparable with the characteristics of biological microarray method (93.9%, 71.8%, 82.9%; p=0.127, p<0.001, p=0.139, respectively).