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The 2022 mpox (formerly monkeypox) outbreak affected predominantly men who have sex with men (MSM), likely through sexual transmission, which resulted in institutions specializing in sexual health being at the frontlines of the mpox outbreak. Fenway Health in Boston serves close to 10 000 MSM annually, which includes more than 2400 MSM who are living with HIV and 3320 MSM with active HIV preexposure prophylaxis (PrEP) prescriptions. We report on the programs implemented and changes to clinical practice at Fenway Health during the mpox outbreak. Fenway Health diagnosed its first case of mpox in June 2022 and treated this patient with tecovirimat. In early July 2022, Fenway Health administered its first dose of the Jynneos vaccine under the Emergency Use Authorization for protection against mpox. As of October 6, 2022, 69 people had tested positive for the mpox virus at Fenway Health. Among the 69 people who tested positive, 43 (62.3%) self-identified as male, with the remaining not reporting a sex or gender identity, and 40 (58.0%) reported their sexual orientation as gay or bisexual. Twenty-five people (36.2%) were treated with tecovirimat. As of October 30, 2022, Fenway Health had administered 6376 doses of the Jynneos vaccine. The programmatic changes involved in rollout and scale-up of vaccination, treatment, and community outreach services at Fenway Health during the 2022 mpox outbreak that we describe here could inform strategies to address subsequent outbreaks. [ABSTRACT FROM AUTHOR]