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This study delved into the composition of ticks, prevalence of Theileria parva and management of East Coast Fever in Nakaseke and Nakasongola districts of Uganda. The tick challenge on animals was assessed and whole blood was collected for determination of seroprevalence of Theileria parva using Enzyme-Linked Immunosorbent Assay. Majority (82.3 percent) of the cattle were found to be infested with Rhipicephalus appendiculatus (88.2 percent), Ambryomma variegatum (7.5 percent) and Rhipicephalus evertsi (4.3 percent). Majority (80.7 percent) of the respondents believed that tick infestation was severe and regularly managed using acaricides (65.3 percent). In the pastoral farming system, no ticks were found on calves below 6 months of age. In the mixed crop-livestock farming system, all cattle age groups were exposed to the ticks. The seroprevalence of T. parva varied among age groups of cattle in both farming systems. There was moderate correlation between the mean number of R. appendiculatus ticks and seroprevalence of T. parva (r = 0.47). Association was established between mean number of ticks and farming system (p = 0.019) and percentage positivity of T. parva and farming system (p = 0.007). Theileria parva was prevalent in the two farming systems despite frequent application of acaricides. Thus, the study provides evidence of the tick-borne disease pathogens and vectors responsible for ECF, R. appendiculatus being the principal tick species infesting cattle in the area. Creation of community-based technical and advisory services for livestock health management is recommended.