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We analyzed data from 2012-2016 for patients who were hospitalized or who died after ≥1 dose of isoniazid-rifapentine for treatment of latent Mycobacterium tuberculosis infection. No patients died; 15 were hospitalized. Nine patients experienced hypotension and 5 had elevated serum aminotransferases, reinforcing the need for vigilant monitoring during treatment. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in