Objective To explore the empirical literature on gender/sex differences in vaccine acceptance among U.S.-based adults and adolescents in approximately the first 2 years of the pandemic. Data source Embase, Medline, PsycINFO, EBSCO, CINAHL, Web of Science Study inclusion and exclusion criteria Peer-reviewed studies conducted in the U.S. with those aged 12 and older, published in English before January 12, 2022, examining the relationship between gender/sex on COVID-19 vaccine intentions and/or uptake. Data extraction Three authors screened studies and extracted data. Data Synthesis Univariate and multivariate results are summarized. Results A total of 53 studies met inclusion criteria (48 intentions, 7 uptake), using mostly cross-sectional designs (92.5%) and non-random sampling (83.0%). The majority of studies supported men’s greater intentions to vaccinate compared to women, and men’s greater vaccine uptake in univariate analyses, but most multivariate analyses supported no gender differences in uptake. Few studies examined gender beyond binary categories (women/men), highlighting a gap in the studies inclusive of transgender or gender-diverse populations in analyses. Conclusion Women may have been more hesitant to get the vaccine than men early in the pandemic, but these differences may not translate to actual behavior. Future research should include non-binary/transgender populations, explore the gender-specific reasons for hesitancy and differences by sub-populations, utilize more rigorous designs, and test gender-sensitive public health campaigns to mitigate vaccine concerns.