OBJECTIVES: Drug-resistant tuberculosis (DR-TB) is a major public health issue with suboptimal outcomes and significant costs despite prolonged treatment. Bedaquiline provides clinical benefits without toxicity of older drugs and has the potential to improve treatment success and cost effectiveness. We compared the cost-effectiveness of bedaquiline regimens with standard-of-care injectable regimens in India, Russia, and South Africa, which represent diverse healthcare settings and TB epidemiology profiles and account for 52% of the global DR-TB burden. METHODS: A 5-year cost-effectiveness model compared direct costs of DR-TB treatment with short- and long-course regimens (SCR and LCR) including bedaquiline or standard-of-care injectables. Costs included drug, hospitalization, ototoxicity, nephrotoxicity, diagnostic/monitoring, anemia, surgical, and end of life. Additionally, scenarios which altered regimen costs, choice of injectable, SCR/LCR usage rates, and conversion rate to bedaquiline were evaluated. RESULTS: Bedaquiline provides improved clinical benefits (efficacy, mortality, AEs) and cost effectiveness over standard-of-care injectables in both the SCR and LCR. Cost savings are most significant in the LCR, where bedaquiline-regimen savings for 2018 were $106,392, $6,419, and $7,879 in cost per treatment success for Russia, India and South Africa, respectively. Similarly, in the SCR it provides savings of $456 and $997 for India and South Africa, respectively. In both SCR and LCR, the higher treatment success rate associated with bedaquiline is the primary cause of lower hospitalization and adverse event-related costs. Bedaquiline regimens also avoid ototoxicity and nephrotoxicity related to injectables, which are significant patient burdens. CONCLUSIONS: Bedaquiline regimens enable improved treatment success rates and cost effectiveness in Russia, India, and South Africa. Higher drug costs for bedaquiline-containing regimens are offset by improved treatment success rates, significantly lowering hospitalization (driven by accelerated sputum culture conversion) and adverse event-related costs. Accelerated adoption of bedaquiline in both SCR and LCR, may optimize health system DR-TB costs and improve patient outcomes.