Background: Progressive disseminated histoplasmosis (PDH) is an endemic disease in most of Latin America, especially among patients with HIV. There are few reports about this disease in Peru. Aims: To describe the clinical, epidemiological and mycological features of patients with PDH and HIV evaluated in a tertiary hospital. Methods: A retrospective study to find out the data of patients diagnosed with PDH and HIV in the period 2000–2019 was carried out. For the statistical analysis of quantitative variables, measures of central tendency and dispersion were used; for the qualitative variables, absolute and relative frequencies were used. Results: Forty-three male patients with PDH were diagnosed in the study period, with a median age of 33 years (IQR: 29–38 years) and a median CD4 lymphocytes count of 39 cells/mm3 (IQR: 20–83 cells/mm3). Eighty six percent of the patients were born or had travelled to the jungle, 58.1% were alcohol users and 16.1% had a history of pulmonary tuberculosis. When compared to histopathology, the culture had a better sensitivity to achieve a diagnosis (p < 0.05). Conclusions: Peruvian patients with PDH and HIV infection were mainly young male adults that were born or had travelled to the jungle, with a CD4 count below 100 cells/mm3. In patients with the described characteristics it would be advisable to check for PDH. Implementing rapid diagnostic tests is also necessary.