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Abstract Background The cost of treating and managing cases of active tuberculosis (TB) disease—from diagnosis to treatment completion—is needed by agencies working on public health budgets, resource allocation and cost-effectiveness analysis. Although components of TB costs have been published in the United States (US), no recent study has assessed overall costs for TB care and potential gaps. To systematically review the US literature for costs of treating and managing cases of active TB disease, adjust these costs to current (2015) values, and assess gaps. We quantified total direct costs—from the perspective of the health care payer—of the treatment and case management of active TB disease. Estimates were based on published figures in the US, and operational data of the California Department of Public Health. Result The average direct cost of treating and managing a TB case was $34,600 in 2015. The average cost of a multidrug-resistant TB case was $110,900. Health care spending for treating and case managing TB patients in California amounted to approximately $75.6 million for the 2133 new cases reported in 2015. Most published cost estimates were based on data from the 1990s. Conclusion TB is resource-intensive to treat and manage. Our synthesis provides inputs for budgets and economic analyses. New studies to provide original cost data are needed to better reflect current clinical and public health practices.