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Zenebe Tefera, Mandefro Assefaw Department of Midwifery, College of Medicine and Health Sciences, Wollo University, Dessie, EthiopiaCorrespondence: Zenebe Tefera, Wollo University, P.O. Box 1145, Dessie, Ethiopia, Tel +251921397834, Fax +251331124352, Email zenebe7834@gmail.comBackground: The World Health Organization recommends that pregnant women should receive a vaccine against COVID-19. However, COVID-19 vaccine hesitance was one of the barriers to delivering the vaccine, and this issue was not well addressed in Ethiopia. Therefore, we aimed to determine the prevalence of COVID-19 vaccination acceptability and the factors that influence it among pregnant women in Northeast Ethiopia.Methods: A mixed-methods approach comprising both qualitative interviews and a quantitative survey was conducted from January 1– 30, 2022. For the quantitative part, a multi-stage sampling technique was used to recruit the study participants (n=702). Data was collected through face-to-face interviews using pretested and structured questionnaires. Bivariate and multivariable logistic regression analyses were employed. The statistical difference was considered at P-0.05, and the strength of association was assessed by the odds ratio and respective 95% confidence intervals. For the qualitative part, 18 participants were selected purposively for in-depth interviews, an interviewer guide was used for data collection and thematic content analysis was performed.Results: In this study, a total of 702 pregnant women were included with the response rate of 100%. The rate of COVID-19 vaccine acceptance was 22.6% (95% CI: 19.6%, 25.9%). The husbands’ educational level (AOR = 1.99, 95% CI: 1.09, 3.64), chronic medical illness (AOR = 2.41, 95% CI: 1.28, 4.54), positive attitude (AOR = 1.59, 95% CI: 1.09, 2.31), and good practice of COVID-19 preventive measures (AOR = 1.59, 95% CI: 1.09, 2.31) were determinant factors of COVID-19 vaccine acceptance. According to the qualitative findings, the most common reasons for COVID-19 vaccine hesitancy were fear of fetal side effects, misconceptions about the vaccine, and religious beliefs.Conclusion: In this study, the acceptability of the COVID-19 vaccine was low. Therefore, health professionals should disseminate accurate vaccination information and address misinformation to boost vaccine acceptance among pregnant women.Keywords: COVID-19 vaccine, a mixed method, pregnant women, Northeast Ethiopia