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Objective To assess spatiotemporal trends in, and determinants of, the acceptance of coronavirus disease 2019 (COVID-19) vaccination globally, as expressed on the social media platform X (formerly Twitter). Methods We collected over 13 million posts on the platform regarding COVID-19 vaccination made between November 2020 and March 2022 in 90 languages. Multilingual deep learning XLM-RoBERTa models annotated all posts using an annotation framework after being finetuned on 8125 manually annotated, English-language posts. The annotation results were used to assess spatiotemporal trends in COVID-19 vaccine acceptance and confidence as expressed by platform users in 135 countries and territories. We identified associations between spatiotemporal trends in vaccine acceptance and country-level characteristics and public policies by using univariate and multivariate regression analysis. Findings A greater proportion of platform users in the World Health Organization's South-East Asia, Eastern Mediterranean and Western Pacific Regions expressed vaccine acceptance than users in the rest of the world. Countries in which a greater proportion of platform users expressed vaccine acceptance had higher COVID-19 vaccine coverage rates. Trust in government was also associated with greater vaccine acceptance. Internationally, vaccine acceptance and confidence declined among platform users as: (i) vaccination eligibility was extended to adolescents; (ii) vaccine supplies became sufficient; (iii) nonpharmaceutical interventions were relaxed; and (iv) global reports on adverse events following vaccination appeared. Conclusion Social media listening could provide an effective and expeditious means of informing public health policies during pandemics, and could supplement existing public health surveillance approaches in addressing global health issues. [ABSTRACT FROM AUTHOR]