Death from Rocky Mountain spotted fever (RMSF) is preventable with prompt, appropriate treatment. Data from two independent sources were analyzed to estimate the burden of fatal RMSF and identify risk factors for fatal RMSF in the United States during 1999-2007. Despite increased reporting of RMSF cases to the Centers for Disease Control and Prevention, no significant changes in the estimated number of annual fatal RMSF cases were found. American Indians were at higher risk of fatal RMSF relative to whites (relative risk [RR] = 3.9), and children less than 10 years of age (RR=5.1) [corrected] and adults ≥ 70 years of age (RR = 3.0) were also at increased risk relative to other ages. Persons with cases of RMSF with an immunosuppressive condition were at increased risk of death (RR = 4.4). Delaying treatment of RMSF was also associated with increased deaths. These results may indicate a gap between recommendations and practice.