Fifty-four episodes of Xanthomonas maltophilia infection were observed in 52 HIV-infected patients out of 2062 assessed (2.52%) over a 6-year period: sepsis/bacteraemia in 44 cases, lower airways infection in 5 cases, urinary tract infection and pharyngitis in 2 cases each, and lymph node involvement in one patient. X. maltophilia represented the fourth most common non-mycobacterial bacterial pathogen responsible for bacteraemia in HIV-infected patients: 44 cases out of 721 diagnosed (6.1%). When compared with non-typhoid Salmonella spp. bacteraemia, an increased risk to develop X. maltophilia disseminated infection was seen according to the progression of HIV-related immunodeficiency, the occurrence of leukopenia-neutropenia, central venous catheterization, previous antibiotic and/or corticosteroid treatment, and hospitalization. In 3 patients suffering from concurrent AIDS-related disorders, X. maltophilia infection contributed to death, while a recurrence occurred in 2 cases only. Due to the poor antimicrobial susceptibility of this pathogen (also confirmed in our series), X. maltophilia bacteraemia associated with advanced HIV infection and concurrent risk factors, may represent a potentially severe disease.