BackgroundThe availability of an effective vaccine does not equate to its use; its effectiveness primarily depends on vaccine acceptance by the targeted population. Despite the rapid development and widespread access to the COVID-19 vaccine, herd immunity is yet to be achieved, with vaccine hesitancy as a major barrier. This study sought to systematically assess the beliefs, attitudes, and acceptance towards COVID-19 vaccines, including factors contributing to vaccination hesitancy in the Eastern and Western hemispheres.MethodsA comprehensive search of articles was conducted through Scopus, PubMed, Embase, CINAHL, Cochrane CENTRAL, and Web of Science databases for studies published from inception to May 2023 using the PRISMA guidelines.ResultsOur search yielded 1154, of which 21 were eligible for inclusion. The rate of willingness or intention to vaccinate varied with the geographic region, from 12% in the USA to 93.9% in China. Four studies from the Western and two from Eastern regions reported a low acceptance rate (defined as <50%): USA (12%), Spain (48.3%), Switzerland (38.6%), Europe (multi-national, 31%), Nepal (38.3%), and Oman (43%). Overall, vaccine acceptance was low-to-moderate in the general population and healthcare workers (HCWs) in both Eastern and Western hemispheres except for China which reported high acceptance (defined as >75%) among the general population and HCWs. Demographic characteristics (female, younger age, and higher education) and non-demographic factors (knowledge about the COVID-19 vaccine and its development, history of influenza vaccination, perceived susceptibility or severity of infection, and the belief that vaccines are effective in controlling the pandemic were associate with high acceptance rates or intentions to take the COVID-19 vaccine. On the other hand, mistrust of the vaccine, its safety and effectiveness, disinformation or poor awareness of the vaccine, side effects concerns, belief in natural immunity, previous adverse experience with the vaccines, and distrust in the information sources about the COVID-19 pandemic were associated with vaccination hesitancy.ConclusionFor better acceptance, COVID-19 vaccination campaign strategies should be modeled based on regional political, economic, and social contexts.HighlightsThe willingness to accept COVID-19 vaccines was low-to-moderate in both hemispheres.Healthcare workers were as willing to vaccinate as the general population.Vaccine hesitancy was associated with demographic and vaccine-specific factors.