Vaccine hesitancy (VH) is defined as a delayed in acceptance or refusal of vaccines despite availability of vaccination services. This multinational study examined user interaction with social media about COVID-19 vaccination. The study analyzed social media comments in 24 countries from five continents. In total, 5856 responses were analyzed; 83.5% of comments were from Facebook, while 16.5% were from Twitter. In Facebook, the overall vaccine acceptance was 40.3%; the lowest acceptance rates were evident in Jordan (8.5%), Oman (15.0%), Senegal (20.0%) and Morocco (20.7%) and the continental acceptance rate was the lowest in North America 22.6%. In Twitter, the overall acceptance rate was (41.5%); the lowest acceptance rate was found in Oman (14.3%), followed by USA (20.5%), and UK (23.3%) and the continental acceptance rate was the lowest in North America (20.5%), and Europe (29.7%). The differences in vaccine acceptance across countries and continents in Facebook and Twitter were statistically significant. Regarding the tone of the comments, in Facebook, countries that had the highest number of serious tone comments were Sweden (90.9%), USA (61.3%), and Thailand (58.8%). At continent level, serious comments were the highest in Asia (58.4%), followed by Africa (46.2%) and South America (46.2%). In Twitter, the highest serious tone was reported in Egypt (72.2%) while at continental level, the highest proportion of serious comments was observed in Asia (59.7%), followed by Europe (46.5%). The differences in tone across countries and continents in Facebook and Twitter and were statistically significant. There was a significant association between the tone and the position of comments. We concluded that the overall vaccine acceptance in social media was relatively low and varied across the studied countries and continents. Consequently, more in-depth studies are required to address causes of such VH and combat infodemics.