Background: Vaccine hesitancy has become an important concern to public health as it carries both individual and community level risks; however, it lacks proper assessment till date. Understanding the burden and the reasons for the same thus becomes a key for an effective solution toward the COVID vaccination among the indigenous tribal community. methods A community based sequential explanatory mixed methodsstudy was conducted among 238 eligible indigenous Khasi tribes of Meghalaya, North East India.  The quantitative part involved a cross-sectional study to determine the proportion of vaccine hesitancy and the qualitative part comprised of in-depth interviews among the eligible residents and key informant interview among the health workers providing the vaccination services, to explore the facilitators and barriers of vaccine uptake. Results: A total of 113 [47.5% (95% CI: 41.0%-54.0%)] participants were found to be hesitant to vaccination, among which 40 [16.8% (95% CI: 12.4%-22.3%) were initially hesitant and 73 [30.7% (95% CI: 24.9%-37.0%) had vaccine refusal. The themes generated through qualitative interviews were individual related, disease related, vaccine related, healthcare system and provider related and socio-cultural and religious. The main barriers were identified under perceived susceptibility and perceived severity under the individual perception along with ambiguity aversion, scepticism about the efficacy, mistrust, concerns on side effects, rumours and socio-cultural and religious misbeliefs acting as major perceived barriers for likelihood of action. Some of the facilitators were literacy, health consciousness, family motivation and perceived benefit on effectiveness. Conclusions: and recommendations: Vaccine hesitancy is found to be relatively higher for the indigenous tribes and it depends on complacency towards the vaccine, confidence on its safety, perceived susceptibility and severity to the disease coupled with modifying factors for cues for action. Healthcare workers should better communicate to improve the uptake of vaccine by reducing the barriers on the vaccine acceptance.