ObjectiveA key challenge towards a successful COVID-19 vaccine uptake is vaccine hesitancy. We examine and provide novel insights on the key drivers and barriers towards COVID-19 vaccine uptake.DesignThis study involved an anonymous cross-sectional online survey circulated across the UK in September 2020. The survey was designed to include several sections to collect demographic data and responses on (1) extent of agreement regarding various statements about COVID-19 and vaccinations, (2) previous vaccination habits (eg, if they had previously declined vaccination) and (3) interest in participation in vaccine trials. Multinominal logistic models examined demographic factors that may impact vaccine uptake. We used principle component analysis and text mining to explore perception related to vaccine uptake.SettingThe survey was circulated through various media, including posts on social media networks (Facebook, Twitter, LinkedIn and Instagram), national radio, news articles, Clinical Research Network website and newsletter, and through 150 West Midlands general practices via a text messaging service.ParticipantsThere were a total of 4884 respondents of which 9.44% were black, Asian and minority ethnic (BAME) group. The majority were women (n=3416, 69.9%) and of white ethnicity (n=4127, 84.5%).ResultsRegarding respondents, overall, 3873 (79.3%) were interested in taking approved COVID-19 vaccines, while 677 (13.9%) were unsure, and 334 (6.8%) would not take a vaccine. Participants aged over 70 years old (OR=4.63) and the BAME community (OR=5.48) were more likely to take an approved vaccine. Smokers (OR=0.45) and respondents with no known illness (OR=0.70) were less likely to accept approved vaccines. The study identified 16 key reasons for not accepting approved vaccines, the most common (60%) being the possibility of the COVID-19 vaccine having side effects.ConclusionsThis study provides an insight into focusing on specific populations to reduce vaccine hesitancy. This proves crucial in managing the COVID-19 pandemic.