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Vaccination is a key public health strategy that is known to be effective in mitigating the risk of infection and severe disease. However, in the context of the COVID-19 pandemic, the percentage (<50%) of Malaysians who have received a booster for the COVID-19 vaccine has remained stagnant over a year. This study aimed to determine the prevalence of and the factors associated with hesitancy toward the second dose of booster for the COVID-19 vaccine. A web-based cross-sectional study was conducted from August to November 2022. The Oxford Vaccine Hesitancy Scale was used to assess the hesitancy toward the second dose of booster for the COVID-19 vaccine. Simple and multiple factors logistic regressions were used to determine the predictors of hesitancy. A p-value less than 0.05 was considered to be statistically significant. Data from 798 respondents were included in the analysis. The prevalence of hesitancy toward the second booster of the COVID-19 vaccine was 26.7%. The predictors of second-booster hesitancy were older age (AOR = 1.040, 95 CI = 1.022, 1.058), having received the third dose (first booster) because of instruction by the government (AOR = 2.125, 95% CI = 1.380, 3.274), concern about serious long term side effects of the vaccine (AOR = 4.010, 95% CI = 2.218, 7.250), and opinions of close friends and immediate family members that the booster is harmful (AOR = 2.201, 95% CI = 1.280, 3.785). Conversely, factors that appear to reduce vaccine booster hesitancy were acceptance of the third dose due to the high number of cases and the increasing rate of infection (AOR = 0.548, 95% CI = 0.317, 0.947), the belief that the vaccine will decrease the risk of getting the infection (AOR = 0.491, 95% CI = 0.277, 0.870), and opinions of close friends and immediate family members that the booster is helpful (AOR = 0.479, 95% CI = 0.273, 0.840). In conclusion, more than one-fifth of Malaysians were hesitant to take the second booster of the COVID-19 vaccine. This suggests that appropriate steps that increase vaccine acceptance, taking into consideration the findings of the present study, are needed to address this issue and to foster more positive attitudes toward vaccination. The survey was available in three main languages but limited to people with internet access; hence, it would likely be biased toward younger adults and social media users and exclude those with limited or no internet access, in particular older people. Therefore, the results are not representative of the Malaysian population at large and caution should be exercised when interpreting the findings. [ABSTRACT FROM AUTHOR]