This project was designed to define the prevalence and associated risk factors of ticks and tick-borne theileriosis and comparative efficacy of various over-the-counter acaricidal and anti-theilerial compounds at the small holder dairy farming system of district Toba Tek Singh (T.T. Singh), Punjab, Pakistan. Questionnaire based stratified random sampling was used for the screening of animals. Blood and tick samples were collected from 4608 animals for assessing the level of theilerial infections in both tick and host population during November 2010 to October 2012. The overall prevalence of ticks was recorded 52.14% (2403/4608) in cattle and buffaloes of study area. However, the abundance was found significantly higher in cattle as compared with buffaloes. Among the identified species of ticks, Hyalomma (H.) anatolicum (a.) anatolicum was found significantly predominant followed in order by Rhipicephalus (R.) microplus and R. sanguineus. The overall theilerial infection in the acini of tick salivary glands was recorded 20.85% (1126/5400). H. a. anatolicum (62.56%; 1126/1800) was the only infected tick specie in the study area. Methyl pyronine green (MPG) stain, female ticks, riverine area, infesting attitude and cattle specie were found having positive association with theilerial infections in tick acini. The overall prevalence of bovine tropical theileriosis was found 49.87% (2298/4608) in cattle and buffaloes of the study area with higher prevalence in cattle. Theileria (T.) annulata was the only prevalent specie. Among various associated determinants of a) host, Friesian breed of cattle, Kundi breed of buffaloes, female sex, young age and cattle population b) microclimate, grazing system, tethering of animals, close housing, poor hygienic measures, mixed farming practices, un-cemented floor pattern, pond watering system, tehsil Kamalia and c) macroclimate, rainy season were found having positive correlation with the bovine tropical theileriosis. Hematological analysis showed statistically a significant decrease in mean haemoglobin concentration, packed cell volume, mean corpuscular hemoglobin concentration, red blood cells count, white blood cells count, neutrophils (P<0.001), serum total bilirubin and active serum enzyme, while a significant increase was recorded in lymphocyte count (P<0.001), corpuscular volume, serum total protein and albumin. Participatory epidemiological investigation revealed highest trend of farmers towards the quacks for consultancy and their therapeutic concerns towards ethnoveterinary medicine with Decoctions as drug of choice. The combined effect of ivermectin and buparwaquone was found the best in order followed by amitraz + oxytetracyclene and cypermethrine + Calotropis procera. The total economic losses of 3.23 million rupees have been calculated in the present study.