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Background: In the midst of the global COVID-19 vaccine distribution challenge, religion stands out as a key determinant of vaccine hesitancy and health choices. Notably, the multifaceted religious environments of Africa and the Asia Pacific remain under-researched in this context., Methods: Utilizing data from two survey waves conducted between 2021 and 2022, this cross-sectional study investigated the effects of religious beliefs on perceptions of compatibility between religion and vaccines and COVID-19 vaccine acceptance in Africa and Asia Pacific. Logistic regression models were employed, with interaction terms between socio-economic factors incorporated to account for variations among diverse subpopulations., Results: Among the eight religious groups identified, Atheists and Buddhists in the Asia Pacific exhibit the lowest agreement, with fewer than 60% acknowledging the religious compatibility of vaccines. Willingness to accept vaccines, however, is consistently higher in Asia Pacific by at least four percentage points compared to Africa, with the disparity widening further in the second wave. Impacts of education on vaccine perceptions vary across religious groups, while acknowledging vaccine compatibility with religion positively contributed to vaccine acceptance. Dynamics between region, religion, and other socio-demographic factors have changed substantially over time. All but Atheists and Muslims exhibit a higher propensity to endorse vaccines during Survey Wave 2., Conclusions: Our study reveals complex, context-dependent connections between vaccine attitudes and religion and the heterogeneous effects of time and education among different religious affiliations. Understanding the underlying drivers of these temporal variations helps inform tailored approaches aimed at addressing vaccine hesitancy, promoting vaccine uptake, and improving the well-being of each religious group., (© 2024. The Author(s).)