This study aims to examine whether and how user-generated comments and reaction emojis on COVID-19 vaccine-promoting Facebook posts induce psychological reactance to posts and vaccine hesitancy in audiences of the posts. An online experiment including 465 American adults showed that, compared with COVID-19 vaccine promotion posts accompanied by pro-vaccine comments, those accompanied by anti-vaccine comments provoked greater reactance in audiences through the mediating effects of bandwagon perception and the presumed influence of the posts on others. Greater reactance, in turn, increased audiences' COVID-19 vaccine hesitancy. Additionally, reaction emojis altered the comments' effects such that pro-vaccine comments triggered less reactance than anti-vaccine comments when the pro-vaccine comments were accompanied by agreement emojis (i.e., “like” and “love”); whereas there was no significant difference between pro-vaccine comments and anti-vaccine comments in reactance when the pro-vaccine comments were accompanied by rejection emojis (i.e., “angry” and “sad”). Furthermore, audiences’ pre-existing attitudes did not affect the effects of opinion cues on their′ reactance and vaccine hesitancy.