BACKGROUND: Only 63% of patients initiating multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment in 2020 were treated successfully. 24-Week all-oral bedaquiline, pretomanid, and linezolid (BPaL)-based regimens have demonstrated higher rates of treatment success and have been recommended by the World Health Organization. Operational research is urgently required to evaluate these regimens in non-trial settings. METHODS: This was a prospective cohort study of patients with microbiologically confirmed MDR/RR-TB and pre-extensively drug-resistant TB (pre-XDR-TB) initiated on BPaL-based regimens in Belarus and Uzbekistan (February 2022-June 2023). All clinical care and research procedures were delivered by treating physicians. After treatment completion, patients were followed up at 6 and 12 months, including collecting sputum to ascertain recurrence. The primary objective was to estimate the effectiveness (cured or treatment completed) and safety (the occurrence of serious adverse events) of BPaL-based regimens. RESULTS: A total of 677 patients initiated treatment with BPaL-based regimens during the study. We documented successful treatment outcomes in 95.3% (427/448) of patients with MDR/RR-TB treated with BPaL plus moxifloxacin and 90.4% (207/229) of patients with pre-XDR-TB treated with BPaL plus clofazimine. 10.2% (69/677) experienced serious adverse events including 24 deaths (3.5%), 11 of which occurred during treatment. 83.3% (20/24) of deaths were not related to TB or TB treatment. Of patients who were successfully treated and completed 12-month follow-up, 0.5% (2/383) had recurrence. CONCLUSIONS: BPaL-based regimens for MDR/RR-TB and pre-XDR-TB are safe and highly effective in non-trial settings. These regimens should be considered for widespread implementation globally, and further research is needed to evaluate their performance in other key populations.