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In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemken, Ethiopia, a highland region where only few cases had been reported before. We analyzed records of VL patients treated from May 25, 2005 to December 13, 2007 by the only VL treatment center in the area, maintained by Médecins Sans Frontières-Ethiopia, Operational Center Barcelona-Athens. The median age was 18 years; 77.6% were male. The overall case fatality rate was 4%, but adults 45 years or older were five times as likely to die as 5–29 year olds. Other factors associated with increased mortality included HIV infection, edema, severe malnutrition, pneumonia, tuberculosis, and vomiting. The VL epidemic expanded rapidly over a several-year period, culminating in an epidemic peak in the last third of 2005, spread over two districts, and transformed into a sustained endemic situation by 2007.