Mastitis is one of the most economically important diseases of dairy animals in Pakistan. The cure rate of mastitis with the use of antibiotics/antibacterials leaves a lot to be desired. In addition, the use of these agents leads to undesireable residues in milk and poses a host of problems to milk processing industry. Therefore, measures other than the use of antibiotics/antibacterials are being investigated to improve the mastitis cure rate. Keeping these considerations in perspective, the current study was planned with the objective to evaluate the therapeutic efficacy and cost-effectiveness of autogenous herd and animal-specific mastitis vaccines alone and in combination with antibiotic based rational therapy after investigating the magnitude of clinical and subclinical mastitis in Tehsil Faisalabad. The current study was compartmentalized into 3 parts. In part I of the study, cattle and buffaloes of 19 villages from 59 Union Councils of Tehsil Faisalabad were screened for subclinical mastitis using surf field mastitis test (SFMT) and 10% of the randomly selected clinically and subclinically mastitic quarters were subjected to microbiological examination of milk. Part II of the study envisaged evaluation of herd-specific mastitis vaccines in 3 dairy herds managing at least 50 animals. The mastitic animals of each farm were randomly divided into 3 equal groups.Group 1 received herd-specific mastitis vaccine @ 5ml/animal I/M twice at an interval of two weeks (Protocol I). Group 2 was treated with standard mastitis therapy i.e. Tylosin @ 10mg/kg for three days I/M + amoxicillin & clavulanic acid @ 600 mg I/mm infusion daily for 5 days (Protocol II) whereas Group 3 received combination of herd-specific autogenous vaccine and standard mastitis therapy (Protocol III). Part III of the study aimed at evaluation of animal-specific autogenous vaccines on 60 (clinical n=30; subclinical n=30) cows and buffaloes belonging to small holder farmers and commercial or institutional farms. Evaluation parameters of part II and III of the study included: clinical severity score, SFMT score, clinical and bacteriological cure rate, somatic cell count (SCC), milk quantity and any untoward effect. Cost-benefit analysis of protocol I, II and III was conducted. The data thus generated were analysed using analysis of variance (ANOVA) and Chisquare test, where relevant. Regarding prevalance of mastitis A total of 24467 buffaloes and 13061 cows were screened during this study.A total of 4231 buffaloes and 3256 cows were found to be suffering from mastitis indicating 17.29 and 24.93% prevalence in the respective species. The overall or composite (buffaloes plus cows) prevalence was 19.95%.Whereas regarding occurrence of mastitic pathogens, Staphylococcus aureus was most predominant micoorganism in the locale. A better SFMT based cure rate, clinical cure rate, bacteriological cure rate and significantly reduced somatic cell counts and plate count values were observed in animals which were provided with herd-base or animal base autogenous mastitis vaccine alone or in combination with antibiotic therapy in subcinically or clinically mastitic animals. When cost benefit analysis of the protocol-I was carried out it resulted in an average net profit ofRs.359/animal/day on herd basis, while Rs. 331.75 and 362.65/animal/day for subclinical and clinical mastitis when prepared on animal-specific basis.