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Background and Objectives: Vaccine hesitancy is a big obstacle for vaccination programs, as is anticipated for the COVID-19 vaccination program, resulting in low uptake of vaccines thereby hindering the process of reaching herd immunity. Bearing this in mind the current study was aimed to explore the determinants of vaccine hesitancy amongst the Pakistani population., Methodology: A cross-sectional study was carried out from November 2020 to March 2021. The conceptual framework of the study was based on the 3Cs (Confidence, Convenience, Complacency) model. The google-forms-based questionnaire was disseminated amongst the general population. Data collected were entered into SPSS version 26 and analyzed., Results: Of the 421 participants, 68.4% were women. Non-healthcare workers were 55.8% of respondents. Of vaccine-hesitant individuals, 26.13% reported they were very unlikely to get vaccinated. Perception of COVID-19 vaccine was explored, which revealed 12.6% of individuals agreed the vaccine was not safe as it came out too fast, 50.6% were worried about experiencing side-effects, 18% believed the vaccine will not offer protection and 5.9% believed the vaccine would cause death. Low Practice of standard operating procedure (SOP) in non-Healthcare workers was the strongest contributor to vaccine hesitancy (OR: 5.338, p = 0.040, 95% CI: 1.082-26.330) followed by High complacency (p = 0.026) and Moderate Complacency (OR: 0.212, p = 0.007, 95% CI: 0.069-0.654) towards COVID-19 vaccination. In Healthcare workers the strongest contributor to vaccine hesitancy was having a Moderate Confidence (OR: 0.323, p = 0.042, 95% CI: 0.109-0.958) in the vaccine followed by Moderate Convenience (OR: 0.304, p = 0.049, 95% CI: 0.093-0.993) for vaccination., Conclusion: Campaigning and communication strategies to reaffirm confidence in the COVID-19 vaccine and educating the general population about the vaccine could lead to increased perception of vaccine safety and effectiveness thereby restoring confidence in vaccine and decreasing vaccine hesitancy. Likewise, working to increase vaccine convenience and decreasing complacency towards the COVID-19 vaccine would translate into high vaccine uptake., Mesh Words: Vaccine hesitancy; vaccination intention, COVID-19 vaccine, vaccine confidence, complacency, convenience., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sheikh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)