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Objectives: Monkeypox (Mpox) recent outbreak has changed in terms of predominant transmission route and typical presentation. Describing current epidemiological and clinical characteristics is crucial to identifying cases and halting transmission. Methods: An observational study was conducted at a Peruvian tertiary-level hospital and included all individuals with Mpox virus infection between July 01 and September 03, 2022. Results: Among 205 confirmed cases, 99% (202/205) were men, 94% (192/205) were men who have sex with men or bisexual, and 66% (136/205) were living with HIV. Regarding sexual behavior, 87% (179/205) had a sexual encounter 21 days before consultation, although only 8% (17/205) identified sexual contact with a Mpox confirmed case; 65% (133/205) had sexual intercourse with casual partners, 55% (112/205) reported a last sexual partner unknown, and 21.5% (44/205) continued having sexual intercourse with symptoms. Systemic symptoms were fever (162/205, 79%), malaise (123/205, 60%), headache (119/205, 58%), fatigue (105/205, 52%), and lymphadenopathy (111/205, 54%). The distribution of skin lesions was generalized (166/205, 81%), located in the anogenital area (160/205, 78%), polymorphic (174/205, 85%), and it was the first symptom identified in 46% (94/205) of cases. Overall, 10% (21/205) required hospitalization, of whom 85.7% (18/205) have HIV infection. Complications included bacterial superinfection (n = 18), proctitis (n = 6), balanitis (n = 4), and necrosis of skin lesions (n = 3). Conclusion: In 2022, Mpox mainly affects men who have sex with men and People living with HIV/AIDS. It presents with skin lesions localized to the anogenital area and can lead to severe complications requiring hospitalization.