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Background Vaccination against coronavirus disease 2019 (COVID-19) is a cost-effective mitigation strategy against the pandemic. As the COVID-19 vaccine becomes more available, low uptake is now a global threat and understanding the underpinnings in local contexts is a priority for intervention development. We aimed to evaluate behavioural determinants of COVID-19 vaccine acceptance that could inform engagement strategies to improve vaccine uptake in Makoko, an urban slum in Lagos, Nigeria. Methods A population-based case–control study utilized the barrier analysis (BA) approach to evaluate the beliefs and behaviours of 45 'doers' and 45 'non-doers'. The standardized BA tabulation sheet was used to assess differences in the proportions between the two groups to identify significant factors that could be addressed through a behaviour change strategy. Results Perceived social norms (family, friend, healthcare workers) that approve the vaccine and expected vaccine protection against diseases among doers were determinants of behaviour. Perceived poor accessibility, safety concerns, lack of trust, low vaccine efficacy and low susceptibility to the infection were the most important determinants of behaviour among non-doers. Conclusions Measures to improve COVID-19 vaccine acceptance in Makoko should include improvement in accessibility and exposing myths and misinformation through clear, concise and evidence-based community education delivered by trusted persons such as healthcare workers and religious leaders. [ABSTRACT FROM AUTHOR]