Background: Determinants of vaccine acceptance are multifactorial, complex, and in most cases, context-dependent. We determined the prevalence of COVID-19 vaccination intention (VI) and fear of its adverse effects (FAE) as well as their associated factors in Latin America and the Caribbean (LAC). Methods: We conducted a secondary cross-sectional analysis of a database collected by the University of Maryland and Facebook. We included participants aged 18 and over from LAC surveyed, January 15 to February 1, 2021. We evaluated VI, FAE, sociodemographic characteristics, COVID-19 symptomatology, compliance with community mitigation strategies, food and economic insecurity, mental health evaluation and the influence in VI when recommended by different stakeholders. We calculated crude and adjusted prevalence ratios with their 95%CIs. Results: We analyzed 472,521 responses by Latin American adults, finding a VI and FAE prevalence of 80.0% and 81.2%, respectively. We found that female and non-binary genders were associated with a lower probability of VI and a higher probability of FAE. Besides, living in a town, village or rural area and economic insecurity was associated with a higher FAE probability. The fears of becoming seriously ill, a family member becoming seriously ill from COVID-19 and having depressive symptoms were associated with a higher probability of VI and FAE. Conclusion: Eight out of 10 adults in LAC have VI and FAE. The factors identified are useful for the development of communication strategies to reduce FAE frequency. It is necessary to guarantee mass vaccination and support the return of economic activities.