Aim The study was planned to assess the acceptance of the COVID-19 vaccine in pregnant and lactating women and identify the significant hurdles in vaccine acceptance. Material and Method It was a prospective observational, cross-sectional study conducted at the Department of Gynecology and Obstetrics, Kasturba Medical College, Manipal, Karnataka, in April 2021. A self-made questionnaire was prepared to gauge the acceptance and major hurdles of COVID- 19 vaccination among pregnant and lactating women. Upon receiving the subject’s consent to participate in the study, they were then required to respond to the questionnaire. Results: Among 281 participants, 159 (56.6%) women were pregnant, and 122 (43.4%) were lactating. In the study population, 66% (n, 105) of pregnant women and 68% (n, 83) of lactating women were unwilling to take the vaccine. The risk of adverse events with COVID-19 vaccination, chances of pregnancy loss, doctor’s recommendation, and vaccine convenience were significant factors that impacted the acceptance rate of COVID-19 vaccination. Conclusion Most women were concerned about the risk of COVID-19 vaccination, and only 34.0% were ready to take the vaccine during pregnancy and lactation. Government and health centers should promote awareness regarding the safety and use of the vaccine to avoid unfounded fear and encourage joint decision-making in pregnant and lactating women.