Tick-borne relapsing fever is an acute infectious disease transmitted to humans by Ornithodoros tholozani, and it is a notifiable disease in Kurdistan Province, Iran. This cross-sectional survey was carried out from 2000 to 2004. The main aim of this study was to ascertain the prevalence of tick-borne relapsing fever in Kurdistan Province. The prevalence and incidence of tick-borne relapsing fever was monitored by daily clinical surveillance and by thin and thick blood smears of individuals with a fever. In confirmed cases, there was febrile illness, and spirochetes were identified on smears of peripheral blood. A field survey on presence of Ornithodoros tholozani in Bijar county villages was carried out and investigated for the detection of Borrelia spp. A total number of 97 cases including 88 cases from rural areas and 9 cases from urban areas were recorded over 5 years. Epidemiological studies on O. tholozani ticks collected from the several locations of villages indicated that 2 of the 20 studied villages (10%) were infested by the vector tick, O. tholozani. The presence of O. tholozani in most villages investigated and its infection rate suggest that tick-borne relapsing fever is a common cause of fever in most rural areas of Kurdistan Province. Results of the study demonstrate that tick-borne relapsing fever is under-recognized and under-reported, and the pathogens may be wrongly identified as malaria parasites. The study showed that tick-borne relapsing fever should be considered as an important public health priority in the study area.