American Indians are at greater risk for Rocky Mountain spotted fever (RMSF) than the general U.S. population. The epidemiology of RMSF among American Indians was examined by using Indian Health Service inpatient and outpatient records with an RMSF International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis. For 2001-2008, 958 American Indian patients with clinical diagnoses of RMSF were reported. The average annual RMSF incidence was 94.6 per 1,000,000 persons, with a significant increasing incidence trend from 24.2 in 2001 to 139.4 in 2008 (P = 0.006). Most (89%) RMSF hospital visits occurred in the Southern Plains and Southwest regions, where the average annual incidence rates were 277.2 and 49.4, respectively. Only the Southwest region had a significant increasing incidence trend (P = 0.005), likely linked to the emergence of brown dog ticks as an RMSF vector in eastern Arizona. It is important to continue monitoring RMSF infection to inform public health interventions that target RMSF reduction in high-risk populations.