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SETTING: Madang Province is located on the northern coast of Papua New Guinea (PNG), a critical mixing point between the populous highlands and more remote regions. Madang Province faces challenges with limited capacity to diagnose and treat TB. OBJECTIVE: To describe the TB caseload and investigate factors associated with known unfavourable treatment outcomes. DESIGN: This is a retrospective cohort study using routinely collected TB programmatic data for treatments commenced 1 January 2019 to 31 December 2021. Using multivariable logistic regression, factors associated with known unfavourable treatment outcomes—death, failure after treatment, and loss to follow-up (LTFU)—were evaluated. RESULTS: Of the 4,668 registered and treated, 3,755 had an evaluated outcome, and 33% had unfavourable outcomes, most commonly LTFU (23%). Unfavourable treatment outcomes were significantly associated with HIV-untested (aOR 2.82 compared to HIV-negative; 95% CI 2.39–3.33), having drug-resistant TB (aOR 3.26 compared to drug-susceptible TB, 95% CI 1.18–9.00), and travel time to the health facility 1–<3 hours by foot (aOR 3.53 compared to <1 hour by foot; 95% CI 1.04–12.06). CONCLUSION: High LTFU from TB treatment was associated with factors that indicate barriers to access to care and treatment completion. Decentralisation and strengthening of TB services for improved person-centred care and treatment support are urgently required in Madang Province.