Morbidity and mortality associated with human West Nile virus (WNV) infection is generally attributable to severe neurologic disease; most illness with WNV, however, is characterized by febrile illness. Although generally considered to be a benign, self-limited syndrome, some cases of West Nile Fever (WNF) have been reported as resulting in fatal outcome. We reviewed cause-of-death information for 35 cases of WNF reported as fatal to the Centers for Disease Control and Prevention between 2002 and 2006, to determine underlying primary causes of death and identify groups at highest risk for fatal WNF. Fifteen were determined to be misclassified neuroinvasive disease cases; one death was medically unrelated to WNV infection. Among the remaining 23 cases, the median age was 78 years (range: 54-92), and 78% were >70 years old; the median age for all 13,482 reported cases of WNF during this time period was 47 years (range: 1 month-97 years). Cardiac (8 cases, 35%) and pulmonary complications (6 cases, 25%) were the most common primary causes of death. Underlying medical conditions among fatal WNF cases included cardiovascular disease (13; 76%), hypertension (8; 47%), and diabetes mellitus (6; 35%). Our study suggests that in some individuals, especially persons of advanced age and those with underlying medical conditions, WNF may precipitate death. The elderly are at increased risk of death from both West Nile neuroinvasive disease and WNF, which emphasizes the importance of primary prevention of WNV infection and close monitoring for cardiac and pulmonary complications in elderly patients hospitalized for WNV disease.