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Although rare, disseminated sporotrichosis is increasing in several countries. Despite its limiting toxic potential, amphotericin B is the only intravenous antifungal available to treat severe sporotrichosis. We aimed to describe the effectiveness and safety of amphotericin B treatment for severe sporotrichosis. Clinical records of patients with disseminated sporotrichosis at a reference center were reviewed. This study included 73 patients. Most (53.4%) were men and non-white. HIV coinfection was the main comorbidity (52.1%). Most reported contact with cats (76.7%). Sporothrix brasiliensis was the causative species. Affected sites were skin (98.6%), osteoarticular system (64.4%), upper airway (42.5%), central nervous system (20.5%), eyes (12.3%), and lungs (8.2%). Median doses of amphotericin B used were 750 mg and 4500 mg for deoxycholate and lipid complex formulations, respectively. Amphotericin B discontinuation occurred in 20.5% due to adverse events, mainly azotemia. The outcomes included cure (52.1%), death due to sporotrichosis (21.9%), death due to other causes (9.6%), and loss to follow-up (8.2%). Survival analysis showed an association between cure and the absence of bone, upper airway, and central nervous system involvement. Amphotericin B is the first-choice treatment for disseminated sporotrichosis; however, the severity of systemic dissemination might predict its response. Favorable clinical results depend on prompt diagnosis, investigation of fungal dissemination, and early therapy initiation. [ABSTRACT FROM AUTHOR]