Introduction: The COVID-19 pandemic had a major impact on the health-care system that significantly reduced the capacity to continue delivery of health-care services to common people. Objectives: The study aimed to understand knowledge, anxiety and wiliness about COVID-19 vaccine among frontline health-care workers. Methods: This non-experimental cross-sectional online survey was conducted among frontline health-care workers in India. Snowball sampling technique was used to recruit participants for the study and data were collected through online social media platforms. Independent paired ttest was used to compare between anxiety with exposed to COVID-19, diagnosed with COVID- 19, willingness, and knowledge. Multiple logistic regression model was used to assess the potential effects between the anxiety and other independent variables. Results: Out of 884 responses, 844 respondents were included after removing incomplete and duplicate responses. An association was found between anxiety with age, education, income, and occupation. Except for those diagnosed with COVID-19, other parameters were found significant with anxiety. Similarly on comparison between willingness and not willingness with independent parameter, except for anxiety, all other variables were found significant (P=0.05). Anxiety was found potentially significant with independent variables. Higher anxiety i.e. 0.6 times higher anxiety was found among those exposed to COVID-19, 2.2 times higher anxiety found among those willing to vaccinate, 0.7 times higher anxiety found among those with income less than 10,000, and 0.8 times higher anxiety among those who were student by occupation (p<0.05). Conclusion: Though the vaccinecan boost our immune system and would significantly reduce the strain on the health-care system, It’s important to find ways to keep the stress at bay—not only for emotional wellbeing, but also to make sure to get the full benefits of the vaccine.   Background: The Sever acute respiratory syndrome coronavirus 2(SAR-CoV-2) is the prime causative virus for the COVID-19 on going pandemic. It was reported in December 2019 in Wuhan, China for first time, later spread through the world. The COVID-19 pandemic result in a devasting effect on normal life of human being and it has been claimed millions of lives. Health authorities from the city of Wuhan, China, informed World Health Organization (WHO) about an increase in pneumonia cases of unknown origin on December 31, 2019. Health authorities in China detected novel coronavirus as the causative agent for the pneumonia cases and the virus was initially named “2019-nCoV”, which was later renamed as coronavirus disease 2019 (COVID-19). Owing to the virus virulency and its contagious nature, WHO declared novel coronavirus outbreak a public health emergency of international concern. With the steep rise in number of people infected with the virus outside China, WHO stated the eruption as a pandemic on March 11, 20201. Combating a pandemic would require inter-sectoral co-ordination and vaccine hold one among the key’s to resolve the pandemic crisis. In 2015, the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization outlined vaccine hesitance as a ’time lag in credence or turn down of vaccination despite handiness of vaccination services2 that varies in form and intensiveness based on from where and when it occurs and what vaccine is involved with, as reported in various studies.3, 4 Keywords: COVID-19; Vaccine; Anxiety; Depression; Willingness.