Although visceral leishmaniasis (VL) can affect immunocompromised patients, data from the human immunodeficiency virus (HIV) infection context are limited, and the characteristics of VL in other immunosuppression scenarios are not well defined. A retrospective review of all cases of VL in immunocompromised patients from January 1997 to December 2014 in two Spanish hospitals on the Mediterranean coast was performed. We included 18 transplant recipients (kidney: 7, liver: 4, lung: 3, heart: 2, and blood marrow: 2), 12 patients with other causes of immunosuppression (myasthenia gravis: 3 and rheumatoid arthritis: 2), and 73 VL HIV-positive patients. Fever was more common in transplant patients (94.4%) and patients with other types of immunosuppression (100%) than in HIV-positive individuals (73.3%). Hepatomegaly was less common in transplant recipients (27.8%) and patients with other types of immunosuppression (41.7%) compared with HIV-positive patients (69.9%) (P = 0.01; P = 0.001, respectively). Patients with other types of immunosuppression had a median leukocyte count of 1.5 × 109/L, significantly lower than HIV-positive patients (2.5 × 109/L) (P = 0.04). Serology was more commonly positive in nontransplant immunosuppressed individuals (75%) and transplant recipients (78.6%) than in HIV-patients (13.8%) (P < 0.001). Antimonial therapy was rarely used in transplant recipients (1.9%) and never in patients with other immunosuppressive conditions, whereas 34.2% of HIV-positive patients received it (P = 0.05 and P = 0.01, respectively). Mortality was 16.7% in both transplant recipients and patients with other immunosuppressive conditions and 15.1% in HIV-positive patients. The features of VL may be different in immunosuppressed patients, with more fever and less hepatomegaly and leukopenia than in HIV-infected patients.