Introduction. Information about the primary drug resistance of Mycobacterium tuberculosis to various anti-tuberculosis drugs is important. They are of particular importance for phthisiologists, as they allow determining the optimal regimens for the prevention and treatment of tuberculosis. Aim. To analyze the primary drug resistance of Mycobacterium tuberculosis on the basis of a sample study conducted at the Center of Excellence of the WHO Supranational Reference Laboratories Network at the Central Tuberculosis Research Institute in 2016-2021. Methods. A cross-sectional study of 966 new cases of tuberculosis from 69 subjects of the Russian Federation examined at the Center of Excellence of the WHO Supranational Reference Laboratories Network of the Central Tuberculosis Research Institute. For primary drug sensitivity of Mycobacterium tuberculosis was analyzed material taken before the start of treatment by testing them on liquid nutrient media. Proportions of resistant mycobacteria calculated from the number tested for drug susceptibility, 95% confidence intervals (95% CI). Results. Primary drug resistance: to isoniazid was detected in 585 of 966 - 60.9% at 95% CI [57.7-63.9]; to rifampicin in 443 out of 954 - 46.3%, 95% CI [43.2-49.6]; to ethionamide in 417 out of 966 - 44.2%, 95% CI [40.9-47.6]; to pyrazinamide in 318 out of 791 - 40.8%, 95% CI [37.4-44.3]; to levofloxacin in 246 of 858 - 29.1%, 95% CI [26.1-32.2], to ethambutol in 374 of 856, 43.7%, 95% CI [40.4-47.0], amikacin 202 of 859 had 23.5%, 95% CI [20.8–26.5], capreomycin in 213 of 860, 24.8%, 95% CI [22.0–27.8], moxifloxacin in 239 of 966 - 24.7%, 95% CI [22.1-27.6], linezolid in 13 of 365 - 3.6%, 95% CI [2.1-6.0], bedaquiline 15 out of 276 had 5.4%, 95% CI [3.3–8.8]. Conclusions. The results of the study of the material from newly identified patients from different regions of Russia for the drug sensitivity of Mycobacterium tuberculosis in an international microbiological laboratory suggest a high level of drug resistance exceeding that in its study in regional bacteriological laboratories. It is necessary to consider the expediency of using isoniazid as the only drug for chemoprophylaxis of tuberculosis, as well as the expediency of prescribing treatment regimens for sensitive tuberculosis without prior confirmation of susceptibility of Mycobacterium tuberculosis to at least isoniazid and rifampicin.