Histoplasmosis is the most clinically significant mycosis in Latin America; still it has been neglected in people with human immunodeficiency virus (HIV). There is limited information about its contribution to morbidity and mortality in this population. We conducted a systematic review of scientific literature to provide an estimation of the frequency and mortality of histoplasmosis among people with HIV receiving highly active antiretroviral therapy (HAART) in Latin America, and factors associated with mortality. We searched articles in PubMed, Scopus, WHO Global health library, and Scielo using different combination of terms including "histoplasmosis" and HAART. We identified 949 articles, removed 662 duplicated; screened 287 abstracts; reviewed full text of 53 articles; and selected 15 articles that provided information on the number of patients studied, included patients receiving ART, and reported any measure of frequency estimate for qualitative synthesis. Studies were conducted in Argentina (n = 4), Brazil (n = 6), Colombia (n = 2), French Guyana and the Bahamas (=2), and Guatemala (n = 1). Heterogeneity of studies characteristics precluded any aggregated estimates. Histoplamosis was frequent in these cohort studies and mortality was high despite the use of HAART. Low CD4 counts, delayed HAART initiation and poor adherence were related to increased incidence, poor prognosis and increased mortality, respectively. Histoplasmosis may be an important contributor to mortality in people with HIV in Latin America. Diagnostic delays represent an important limitation for improving care of patients suspected to have histoplasmosis. Reducing histoplasmosis diagnostic delays and therapy initiation is needed to further decrease mortality.