Abstract: Johne’s Disease (JD), caused by Mycobacterium avium subspecies paratuberculosis, is endemic in domestic animals and adversely affects dairy industry worldwide. In the present study, efficacies of ‘Indigenous’and commercial (Gudair, Spain) vaccines were evaluated for control of JD in experimentally challenged goats. Goats were grouped into Sham-immunized, Indigenous and Gudair vaccine groups. Vaccinated kids were challenged at 50 and 270 Days Post Vaccination (DPV), with 3×109 and 5×109 ‘Indian Bison Type strain ‘S 5’, respectively and sacrificed at 150 and 450 DPV after 1st and 2nd challenge, respectively. Vaccines were evaluated for improvements in physical condition (diarrhea, weakness, body coat color), clinical symptoms (shedding of bacilli, mortality, morbidity), immune responses (cell-mediated and humoral), pathology (gross and microscopic lesions) and production status (body weights, growth rates). Vaccinated goats gained higher body weights vis a vis sham-immunized. Mortality was higher in sham-immunized. Cell Mediated Immunity (CMI) response increased at 30 DPV and showed down regulation from 90 DPV onwards in vaccinated goats. Significant increase in humoral immune response was observed in vaccinated goats at 180 DPV and maintained till 450 DPV. Microscopical examination at 180 DPV showed reduced shedding in vaccinated groups, At 200 DPV, group 1 goats showed thickening of small intestine with corrugations specifically at ileocaecal junction, catarrhal enteritis with infiltration of mononuclear cells and epitheloid cells. In vaccinated groups, there were focal thickening of intestines at 450 DPV with lesions of chronic catarrhal enteritis and presence of lymphocyte, plasma cells and macrophages cells with a few epitheloid cells. Monitoring of MAP DNA in the blood of experimental goats of all the groups was done by testing of blood samples by Polymerase Chain Reaction (PCR) and the vaccinated groups of goats revealed MAP bacilli free status upto 300 DPV. Both the vaccines provided protection after challenge I, but since indigenous vaccine also protected goats after challenge II, was therefore superior. In conclusion, the indigenous vaccine must be exploited for its full potential for effective prevention and control of this economically important disease having public health concerns.