Objective : to evaluate the efficacy and safety of a rifapentine-containing regimen in treatment of patients with drug-susceptible respiratory tuberculosis and gastrointestinal comorbidities, compared to the standard 6-8 month regimen. Materials and Methods . An analysis of treatment efficacy and safety was performed in 204 patients with drug-susceptible respiratory tuberculosis who completed a full course of therapy. Inclusion criteria: male and female patients aged 18 years and older, newly diagnosed with respiratory tuberculosis with preserved susceptibility of Mycobacterium tuberculosis to the first line drugs, and concomitant gastrointestinal diseases. Exclusion criteria: HIV infection, acute liver diseases of various etiologies, decompensated liver cirrhosis, grade II–III pulmonary heart failure, and chronic renal failure. Patients in the main group (MG, n=77) received a modified chemotherapy regimen for drug-susceptible tuberculosis, where rifapentine replaced rifampicin in both the intensive and continuation phases. The comparison group (CG, n= 127) received standard chemotherapy regimens. Results . By the end of month 4, sputum culture conversion was achieved in 77.8% of patients in the main group and 46.5% of patients in the comparison group. Lung cavity scarring within 6 months of chemotherapy was observed in 84.4% of patients in the main group, versus 51.5% in the comparison group. Adverse events were reported in 2.6% of patients in the main group and 14.2% in the comparison group (p < 0.05). Conclusion . A modified rifapentine-containing regimen for treatment of drug susceptible tuberculosis is effective and safe in patients with gastrointestinal comorbidities.