Background: Vaccines are highly anticipated for the control of the ongoing COVID-19 pandemic, however their acceptance is critical for the desired benefit. This study assessed risk perception of COVID-19 and acceptability of its vaccine in Nigeria. It also assessed prediction of vaccine acceptance from risk perception. Methods: A cross-sectional web-based study was conducted among 410 participants in the six geo-political regions of Nigeria using a three-part questionnaire developed using Google forms. The questionnaire link was distributed via snowball method to consenting participants through online platforms. Descriptive and inferential statistics (Chi-square and binomial regression) using Microsoft Excel and SPSS version 24 were used to analyze data, and p-values < 0.05 were considered statistically significant.Results: A total of 410 respondents participated in the study and high risk perception of SARS-CoV-2 infection (COVID-19) was seen in 127(66.1%) of respondents. Vaccine acceptance was high in 233(56.8%) of respondents, and was significantly associated with geo-political region (P=0.028). Association between COVID-19 risk perception and vaccine acceptance showed that persons who had high risk perception of COVID-19 may not necessarily accept the vaccine (OR=0.450; 95% CI=0.297–0.683; P=0.000) and this was seen in persons with tertiary education (OR=0.458; 95% CI=0.297-0.706; P=0.000), married (OR=0.194; 955%CI =0.098-0.386; P=0.000), from South-south (OR=0.352; 95%CI=0.163–0.760; P=0.008) and North-central (OR=0.429; 95% CI= 0.189-0.972; P=0.043).Conclusions: High risk perception of COVID-19, and vaccine acceptance were relatively average. Regional and socio-demographic variations were associated with this finding, and it was also noted that high risk perception of COVID-19 may not likely result in vaccine acceptance. Strategic and targeted messaging on vaccine acceptance should be prioritised by stakeholders, to ensure successful vaccine implementation.