Introduction: Histoplasmosis is the most prevalent systemic mycosis in Mexico. However, since 1995, the routine registry of this disease was interrupted in the country; therefore, the current magnitude of the disease is unknown. This study aimedto describe the epidemiological, clinical, and paraclinical characteristics of the histoplasmosis infectionwhich has a wide variety of clinical manifestations -in the population that received care in Mexico's National Institute for Respiratory Diseases. Material and methods:This study used a retrospective design, and the analyzed data were collected from January 2013 to December 2016.We conducted a comparison of characteristics between patients with pulmonary or disseminated forms of histoplasmosis through χ2, Student's T, or Mann-Whitney U tests.Results: In total, 61 patients were included. The average age was 36.1 years ± 12.4; 53 (87%) were men, and the male-female ratio was 6:1. Moreover, 80% of the patients had immunosuppression; 94% had HIV; 50.8% had disseminated histoplasmosis, so it had the most common presentation;and 57% had anemia (i.e. median Hb 10 g/dL). Of the 118 fungus cultures, 74% (87) reported growth. The Histoplasma antigen was positive in 67% (14/21) of the cases, andmortality rate was estimated at 7%. Conclusions:Compared with data published in 1995, we observed a change in the epidemiology and risk factors of histoplasmosis; specifically, there was a lower proportion of occupational exposure and an increase in the number of cases in non-endemic areas (i.e. low risk of transmission). Our results generally corroborate the literature, suggesting that the acquired immunodeficiency syndrome (AIDS) pandemic, the use of immunosuppressant therapy, and the rise in the number of transplants have increased the overall risk of histoplasmosis, even in areas that were not previously identified as endemic. Generally, our studyhighlights the importance of routine registry of this disease in Mexico.