BackgroundThe development of COVID-19 vaccines has been crucial in fighting the pandemic. However, misinformation about the COVID-19 pandemic and vaccines is spread on social media platforms at a rate that has made the World Health Organization coin the phrase infodemic. False claims about adverse vaccine side effects, such as vaccines being the cause of autism, were already considered a threat to global health before the outbreak of COVID-19.ObjectiveWe aimed to synthesize the existing research on misinformation about COVID-19 vaccines spread on social media platforms and its effects. The secondary aim was to gain insight and gather knowledge about whether misinformation about autism and COVID-19 vaccines is being spread on social media platforms.MethodsWe performed a literature search on September 9, 2021, and searched PubMed, PsycINFO, ERIC, EMBASE, Cochrane Library, and the Cochrane COVID-19 Study Register. We included publications in peer-reviewed journals that fulfilled the following criteria: original empirical studies, studies that assessed social media and misinformation, and studies about COVID-19 vaccines. Thematic analysis was used to identify the patterns (themes) of misinformation. Narrative qualitative synthesis was undertaken with the guidance of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 Statement and the Synthesis Without Meta-analysis reporting guideline. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tool. Ratings of the certainty of evidence were based on recommendations from the Grading of Recommendations Assessment, Development and Evaluation Working Group.ResultsThe search yielded 757 records, with 45 articles selected for this review. We identified 3 main themes of misinformation: medical misinformation, vaccine development, and conspiracies. Twitter was the most studied social media platform, followed by Facebook, YouTube, and Instagram. A vast majority of studies were from industrialized Western countries. We identified 19 studies in which the effect of social media misinformation on vaccine hesitancy was measured or discussed. These studies implied that the misinformation spread on social media had a negative effect on vaccine hesitancy and uptake. Only 1 study contained misinformation about autism as a side effect of COVID-19 vaccines.ConclusionsTo prevent these misconceptions from taking hold, health authorities should openly address and discuss these false claims with both cultural and religious awareness in mind. Our review showed that there is a need to examine the effect of social media misinformation on vaccine hesitancy with a more robust experimental design. Furthermore, this review also demonstrated that more studies are needed from the Global South and on social media platforms other than the major platforms such as Twitter and Facebook.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42021277524; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021277524International Registered Report Identifier (IRRID)RR2-10.31219/osf.io/tyevj