Background In drug-resistant tuberculosis (DR-TB) management under India’s programmatic conditions, the World Health Organization (WHO) recommends two all-oral regimens for rifampicin-resistant (RR), multidrug-resistant (MDR), and extensively drug-resistant (XDR) TB: a longer M/XDR-TB regimen (18–20 months) and a shorter bedaquiline-containing MDR/RR-TB regimen (9–11 months). Their comparative effectiveness in India remains under-evaluated. Objective To compare clinical and microbiological outcomes of the longer versus shorter all-oral regimens in a prospective observational cohort. Methods In a prospective observational cohort study from January to December 2022, 906 newly diagnosed MDR-TB patients at a tertiary care center in Lucknow, India, were enrolled—691 on the longer regimen and 215 on the shorter regimen. Six-month culture conversion and final treatment outcomes were recorded. Multivariable logistic regression adjusted for age, sex, baseline smear status, and comorbidities. Results At 6 months, culture conversion was higher with the longer regimen (79.8% vs 67.9%; absolute difference 11.9%; p<0.001; aOR 1.51, 95% CI 1.12–2.04). Favorable treatment outcomes also favored the longer regimen (77.9% vs 69.2%; 8.7%; p=0.010; aOR 1.37, 95% CI 1.05–1.79). In subgroup analyses, differences were significant in pulmonary TB and among women; pulmonary TB independently predicted favorable outcome (aOR 1.46, 95% CI 1.01–2.13). Conclusions In this single-center cohort, the longer all-oral M/XDR-TB regimen yielded superior microbiological and clinical outcomes compared to the shorter regimen. These results support regimen selection tailored by patient profile and resistance pattern, and highlight the need for robust real-world tolerability and safety monitoring.

The authors have declared no competing interest.

No specific funding was received for this study. The kits and consumables provided by the National Tuberculosis Program were used under programmatic settings for routine patient examinations.

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This study was reviewed and approved by the Institutional Ethics Committee of King George’s Medical University, Lucknow, India (Ref No: 126th ECMIIB-Ph.D/P1). All participants provided informed consent in accordance with institutional requirements and national ethical guidelines. All data were de-identified prior to analysis to ensure confidentiality.

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All relevant data underlying the findings of this study are contained within the manuscript and its Supporting Information files. De-identified patient-level data used for analysis are available from the corresponding author upon reasonable request, subject to approval from the Institutional Ethics Committee of King George's Medical University, Lucknow, India, to ensure compliance with patient confidentiality requirements.