Background and aim: A vaccine advisory group to WHO identified complacency, inconvenience in accessing vaccines, and lack of confidence as key reasons underlying hesitancy. Vaccine hesitancy is one of the ten threats to global health in 2019. Hence, the present study was aimed to find out the factors associated with vaccine hesitancy among patients with comorbidities. Material and methods: A Hospital-based cross-sectional study was conducted among 372 patients with comorbiditieswho attended Tagore medical and Dental College and Hospital, Rathinamangalam, Chennai from June 2020 to August 2021 and were willing to participate in the study. A semi-structured interview schedule was used to obtain information on the socio-demographic profile, behavioral risk factors, and covid 19 vaccine details from the study participants. Data were analyzed using SPSS version 21.0. Results: Hypertension was the most prevalent (30%) co-morbidity among the study participants followed by Diabetes (27%).In the present study identified reasons for vaccine hesitancy, there was a statistically significant association with the age group, planning to take it soon, fear of adverse reactions of the comorbidities, not interested/not willing, need to take after specialistconsultation, health issues, and need to discuss with family members.Binary logistic regression was used to determine the association between vaccine hesitancy and possible factors.The odds of vaccine hesitancy among participants aged more than 60 years were 8 times(adjusted OR=8.044, CI: 1.92–33.1) higher than those aged 18 to 24 years. The odds of vaccine hesitancy among participants who had fear of adverse reactions attributed by the participant was 3 times (adjusted OR=2.824, CI: 1.10–7.25) higher than those without fear of adverse reactions.And the odds of vaccine hesitancy for participants who had a need to take after specialist consultation was 6 times (adjusted OR =5.935, CI: 1.52–23.1) higher than those who had after specialist consultation. Conclusion:This study concluded that the majority (23.6%) of the study participants mentioned that they were planning to take the vaccine in the future as the reason for delay followed by fear of adverse reactions attributed by comorbidities (21.2%) and health issues (18.55%).