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The British introduced allopathy medicine in India. Initially, the Western medicine enclave only within the officers and military of British later makes it extend to Indian for several purposes, the only benefit of them in various facets. Here I am trying to reveal the history of the vaccine under the British Raj in Orissa. Oriya speaking people were segmented under the several presidencies viz, Madras, Bengal, and Nagpur administration that south, eastern, and Western Orissa, respectively. Orissa was one of fully clouded state of smallpox in the early colonial rule. Hence the British used a vaccine, especially against smallpox. But the indigenous people were not merely ready to take a vaccine against smallpox, even though the people died of it. Eventually, the British introduced several policies that compulsory as well as sometimes voluntary. The main objective of this paper is trying to understand the administration of vaccination in colonial Orissa. Secondly, how the indigenous people responded to the vaccination administration, this study seeks made use of primary sources of Orissa in public health especially Vaccination reports.