Background: The aim of the study was the assessment of the impact of the molecular genetic Xpert MTB/Rif assay on the diagnostic delay and the treatment effectiveness in pulmonary tuberculosis, according to the results of the microbiological and molecular-genetic methods, in order to optimize the management of the drug resistant tuberculosis. Material and methods: A retrospective selective study, which included 226 patients with multidrug-resistant pulmonary tuberculosis (study sample) and 78 patients with drug-susceptible pulmonary tuberculosis (control group), was performed. Patients were divided into 2 subgroups following the results of the molecular-genetic and bacteriological investigations. The study sample was divided in two groups: the 1st group included 85 patients enrolled in the treatment for drug resistant tuberculosis, according to the results of the Xpert MTB test and the 2nd group included 141 patients enrolled in the treatment DOTS plus, according to the results of the conventional cultures. Results: The impact of the molecular genetic GeneXpert MTB/Rif assay was demonstrated on early diagnosis, adequate treatment according to the drug susceptibility to rifampicin, shorter duration of the treatment, low rate of the side events, optimal treatment compliance and higher treatment effectiveness. The conventional microbiological methods contributed to the late diagnosis of the patients, high rate of the severe and complicated tuberculosis, long duration of the treatment which were reflected on the low treatment effectiveness. However the conventional culture methods allowed the treatment individualization according to the drug susceptibility tests. Conclusions: Target screening of the population with risks and compulsory investigation by GeneXpert MTB/Rif assay will diminish the rate of severe late detected forms of pulmonary tuberculosis and adapt the treatment according to the drug resistance to rifampicin