We describe a man vaccinated with the 17D204 strain of yellow fever virus, who subsequently died of yellow fever. Sequencing of the NS5-39 untranslated region showed that the virus isolated from the patient was identical to the vaccine strain of the same batch, and different from wild-type virus. Both viruses contained a mutation, although the association of this mutation with virulence is unknown. Severe, rapidly progressive, and ultimately fatal disease can follow use of the 17D204 vaccine strain. There is need for renewed discussion as to the safety of the vaccine and the indications for its use.