BACKGROUNDIn February 2022, the U.S. Centers for Disease Control and Prevention (CDC) recommended a 4-month rifapentine-moxifloxacin based regimen (4-HPMZ) for treating drug-susceptible pulmonary TB. We describe 4-HPMZ implementation, treatment outcomes, and regimen tolerability at New York City (NYC) Health Department TB clinics.METHODSA multidisciplinary workgroup developed a 4-HPMZ implementation plan and protocol based on CDC patient eligibility guidance. Treatment outcomes were classified as 'completed' when 4-HPMZ was completed within 5 months or 'discontinued' when 4-HPMZ was stopped due to clinical or programmatic reasons. Adverse events (AEs) included abnormal lab results, or any medication-related concern reported by patients.RESULTSBetween April 2022 to December 2023, 617 patients with TB visited NYC Health Department TB clinics; for 4-HPMZ, 333 (54%) were ineligible and 284 (46%) were eligible. Of the eligible patients, 40 (14%) were prescribed 4-HPMZ; of these, 36 initiated 4-HPMZ treatment, 13 (36%) completed treatment, and 23 (64%) discontinued. A total of 15 patients (42%) discontinued due to AEs.CONCLUSIONSignificant programmatic and clinical challenges were associated with initiation and completion of 4-HPMZ treatment. As a result, few patients completed treatment. Further assessment is needed to identify populations most likely to initiate and complete 4-HPMZ..