Background: Carotid intima‐media thickness (cIMT) has been widely used as a predictor of future cardiovascular disease (CVD); however, various definitions of cIMT exist. This study provides a systematic review and meta‐analysis of the associations between different cIMT definitions and CVD. Methods and results: A systematic review of the different cIMT definitions used in prospective cohort studies was performed. The relationships between cIMT of different definitions (common carotid artery IMT [CCA‐IMT], internal carotid artery IMT [ICA‐IMT], combined segments [combined‐IMT], mean CCA‐IMT, and maximum CCA‐IMT) with future stroke, myocardial infarction (MI), and CVD events were analyzed using random effects models. Among 2287 articles, 18 articles (14 studies) with >10 different cIMT definitions were identified and included in our meta‐analysis. After adjusting for age and sex, a 1‐SD increase in CCA‐IMT was associated with future stroke (hazard ratio [HR], 1.32 [95% CI, 1.27–1.38]), MI (HR, 1.27 [95% CI, 1.22–1.33]), and CVD events (HR, 1.28 [95% CI, 1.19–1.37]). A 1‐SD increase in ICA‐IMT was related to future stroke (HR, 1.25 [95% CI, 1.11–1.42]) and CVD events (HR, 1.25 [95% CI, 1.04–1.50]) but not MI (HR, 1.26 [95% CI, 0.98–1.61]). A 1‐SD increase in combined‐IMT was associated with future stroke (HR, 1.30 [95% CI, 1.08–1.57]) and CVD events (HR, 1.36 [95% CI, 1.23–1.49]). Maximum CCA‐IMT was more strongly related than mean CCA‐IMT with risk of MI, and both measures were similarly associated with stroke and CVD events. Conclusions: Combined‐IMT is more strongly associated with CVD events compared with single‐segment cIMT definitions. Maximum CCA‐IMT shows a stronger association with MI than mean CCA‐IMT. Further research is warranted to validate our findings and to standardize the cIMT measurement protocol, as well as to explore underlying mechanisms.