BACKGROUND: During the COVID-19 pandemic, infodemic spread even more rapidly than the pandemic itself. The COVID-19 vaccine hesitancy has been prevalent worldwide and hindered pandemic exiting strategies. Misinformation around COVID-19 vaccine is a vital contributor to vaccine hesitancy. However, no evidence systematically summarized COVID-19 vaccine misinformation. OBJECTIVE: To synthesize the global evidence on misinformation related to COVID-19 vaccines, including its prevalence, features, influencing factors, impacts, and solutions for combating misinformation. METHODS: We performed a systematic review by searching five peer-reviewed databases (PubMed, EMBASE, Web of Science, Scopus, and EBSCO). We included original articles that investigated misinformation related to COVID-19 vaccine and were published in English from January 1, 2020, to August 18, 2022. We excluded publications that did not cover or focus on COVID-19 vaccine misinformation. The Appraisal tool for Cross-Sectional Studies, Cochrane RoB 2.0 tool, and Critical Appraisal Skills Programme Checklist were used to assess the study quality. The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42021288929). RESULTS: Of 8864 studies identified, 91 observational studies and 11 interventional studies met the inclusion criteria. Misinformation around COVID-19 vaccine covered conspiracy, concerns on vaccine safety and efficacy, no need for vaccine, morality, liberty, and humor. Conspiracy and safety concerns were the most prevalent misinformation. There was a great variation in misinformation prevalence with 2.5~55.4% in general population and 6.0~96.7% in antivaccine/vaccine hesitant groups from survey-based studies, and the prevalence of 0.1~41.3% on general online data and 0.5~56% on antivaccine/vaccine hesitant data from Internet-based studies. Younger age, lower education and economic status, right-wing and conservative ideology, having psychological problems enhanced beliefs in misinformation. The content, format, and source of misinformation influenced its spread. A five-step framework was proposed to address vaccine-related misinformation, including identifying misinformation, regulating producers and distributors, cutting production and distribution, supporting target audiences, and disseminating trustworthy information. The debunking messages/videos were found to be effective in several experimental studies. CONCLUSIONS: Our review provided comprehensive and up-to-date evidence on COVID-19 vaccine misinformation and helps responses to vaccine infodemic in future pandemics.