Background: Over the last decades, several individual studies on sex differences in carotid atherosclerosis have been performed covering a wide range of plaque characteristics and including different populations. This systematic review and meta-analysis aims to summarize previously reported results on sex differences in carotid atherosclerosis and present a roadmap explaining next steps needed for implementing this knowledge in clinical practice. Methods: We systematically searched PubMed, Embase, Web of Science, Cochrane Central, and Google Scholar for eligible studies including both male and female participants reporting prevalence of imaging characteristics of carotid atherosclerosis and meta-analyzed these studies. Studies had to report at least the following: (1) calcifications; (2) lipid-rich necrotic core; (3) intraplaque hemorrhage; (4) thin-or-ruptured fibrous cap; (5) plaque ulceration; (6) degree of stenosis; (7) plaque size; or (8) plaque inflammation. We prespecified which imaging modalities had to be used per plaque characteristic and excluded ultrasonography. Results: We included 42 articles in our meta-analyses (ranging from 2 through 23 articles per plaque characteristic). Men had more frequently a larger plaque compared to women and, moreover, had more often plaques with calcifications (odds ratio=1.57 [95% CI, 1.23–2.02]), lipid-rich necrotic core (odds ratio=1.87 [95% CI, 1.36–2.57]), and intraplaque hemorrhage (odds ratio=2.52 [95% CI, 1.74–3.66]), or an ulcerated plaque (1.81 [95% CI, 1.30–2.51]). Furthermore, we found more pronounced sex differences for lipid-rich necrotic core in symptomatic opposed to asymptomatic participants. Conclusions: In this systematic review and meta-analysis, we demonstrate convincing evidence for sex differences in carotid atherosclerosis. All kinds of plaque features—plaque size, composition, and morphology—were more common or larger in men compared to women. Our results highlight that sex is an important variable to include in both study design and clinical-decision making. Further investigation of sex-specific stroke risks with regard to plaque composition is warranted.