Background. The growth of drug resistance of mycobacterium tuberculosis is a serious problem in the clinical management of patients and disease prevention. Resistance definitions changed periodically. Drug resistance profile for innovative anti-tuberculosis drugs has not studied yet. Purpose: to study the dynamics of the structure of drug sensitivity of Mycobacterium tuberculosis (MBT) among new cases of tuberculosis in the North-Western Federal District (NWFD) in 2010-2021. Assess the readiness of the system of microbiological diagnostics of tuberculosis to implement the current edition of clinical recommendations. Methods. The data of irregular statistical observation were studied: laboratory reports, the results of the response to the request of the Ministry of Health of Russia and the forms of one-time statistical observation for 2021 in the Northwestern Federal District. Results. Retained MBT drug sensitivity in general for the period under review is present in 53.8% (95% CI 53.3-54.4) of new TB cases; while the proportion of such patients decreased from 55.4% to 51.7%. Resistance not requiring the use of second-line drugs was 4.1% (95% CI 3.9-4.3), and also decreased over the period under review from 4.5% to 3.7%. Isoniazid resistance without rifampicin resistance was 10.3% (95% CI 10.0-10.6%) and was not associated with 2nd line drug resistance. Rifampicin resistance in 96.1% was combined with isoniazid resistance. There is a rapid (2.5-fold) increase in drug resistance to rifampicin in combination with fluoroquinolones (from 2.4%; 95% CI 2.2-2.6 to 6.1%; 95% CI 5.6-6, 6). At the same time, drug sensitivity to other drugs also increased. Patients with drug resistance to rifmpicin also had a high proportion of drug resistance to ethambutol (more than 50% in 2021). Only a small part of the laboratories in 2021 determined the drug sensitivity of MBT to bedaquiline and linezolid. The primary broad drug resistance of MBT was 0.05%, and in cases of treatment after an ineffective course of chemotherapy - 0.4%. Conclusion. It is necessary to limit uncontrolled access to fluoroquinolones in order to reduce the growth rate of drug resistance. The frequency of resistance to ethambutol calls into question the appropriateness of its empirical use in cases of tuberculosis treatment with identified resistance to rifampicin. The system of laboratory diagnosis of tuberculosis in 2021 was not ready to implement the updated edition of clinical guidelines due to insufficient coverage of DST for bedaquiline or linezolid. It is required to carry out monitoring trips from the regions of the North-West Federal District with the involvement of specialists in the laboratory diagnosis of tuberculosis.