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Background: Johne’s disease is chronic incurable enteritis mainly responsible for reduced productivity in domestic livestock leading to extensive economic losses to the dairy industry world-wide. Therapeutic efficacy of ’First indigenous vaccine’ developed using novel ’Indian bison type’ biotype of Mycobacterium avium subspecies paratuberculosis (MAP) strain ’s 5’ was evaluated for the treatment of clinical Johne’s disease in the farm herds of Jakhrana breed of goats. Farm herds of this important milch breed of semi-arid region of Rajasthan were endemically infected with Johne’s disease. Materials and Methods: Response to ’Indigenous vaccine’ against Johne’s disease has been studied twice in this farm unit, first time in 2006-07 (Vaccine trail-I) and second time in the present study from 2013-14 (Vaccine trial-II). Data on improvement in health, clinical condition, productivity, reproductive performance, milk yield, survivability, morbidity, mortality, culling and shedding of MAP in feces were recorded before and after vaccination. In vaccine trial-II, 225 adult goats and 70 and 39 kids (above 3 months age) born to un-vaccinated and vaccinated goats were vaccinated one time between 2013 and 2014, respectively. Results: Reduction in shedding of MAP in this vaccine trial-II of infected goats and 1st generation kids was 45.5 and 100.0%, respectively. Presence of MAP in the blood of vaccinated goats was reduced by 23.0% at 360 DPV. Peak titers were achieved around 90 DPV and all vaccinated goats sero-converted by 360 DPV. High to very high morbidity, mortality and cullings encountered before vaccination in the infected Jakhrana goatherds were mainly due to Johne’s disease and were highly reduced after vaccination. Vaccination not only reduced clinical disease but also improved production performance (milk and meat production). Average gain in body weights were distinctly superior in the vaccinated goats and in the 1st generation kids born to vaccinated mothers. After vaccination there was overall improvement in the health of animals, kid survival rate, per animal productivity with respect to milk production and growth rates. Conclusion: Study concluded that ’Indigenous JD vaccine’ developed using native MAP biotype can be employed both for the ’Therapeutic management’ of the disease in the endemically infected goatherds and for the prevention of disease in naive and non-infected goats. The study can serve as model for the utilization of large population of non-productive domestic livestock and for the management and control of incurable Johne’s disease in endemically infected herds and flocks in the country.