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Background: Limb loss leads to significant disability. Prostheses may mitigate this disability but are not readily accessible in low- and middle-income countries (LMICs). Cost-effectiveness data related to prosthesis provision in resource-constrained environments such as Tanzania is greatly limited., Objectives: This study aimed to compare the cost-effectiveness of a prosthesis intervention compared with that of no prosthesis for persons with transfemoral amputations in an LMIC., Study Design: This is a prospective cohort study., Methods: Thirty-eight patients were prospectively followed up. Clinical improvement with prosthesis provision was measured using EuroQuol-5D, represented as quality-adjusted life years gained. Direct and indirect costs were measured. The primary outcome was incremental cost per quality-adjusted life year, measured at 1 year and projected over a lifetime using a Markov model. Reference case was set as a single prosthesis provided without replacement from a payer perspective. Additional scenarios included the societal perspective and replacement of the prosthesis. Uncertainty was measured with one-way probabilistic sensitivity analysis., Results: From the payer perspective, the incremental cost-effectiveness ratio (ICER) was $242 for those without prosthetic replacement over a lifetime, and the ICER was $390 for those with prosthetic replacement over a lifeime. From the societal perspective, prosthesis provision was both less expensive and more effective. One-way sensitivity analysis demonstrated the ICER remained below the willingness to pay threshold up to prosthesis costs of $763., Conclusions: These findings suggest prosthesis provision in an LMIC may be cost-effective, but further studies with long-term follow up are needed to validate the results., (Copyright © 2022 International Society for Prosthetics and Orthotics.)