Purpose To compare common carotid artery (CCA) wall thickness measured manually by using US and semiautomatically by using MRI, and to examine their associations with incident coronary heart disease and stroke. Materials and Methods This prospective study enrolled 698 participants without a history of clinical cardiovascular disease (CVD) from the Multi-Ethnic Study of Atherosclerosis (MESA) from July 2000 to December 2013 (mean age, 63 years; range, 45 to 84 years; same for men and women). All participants provided written informed consent. CCA wall thickness was measured with US as well as both noncontrast proton-density-weighted and intravenous gadolinium-enhanced MRI. Cox proportional hazards models were used to assess the associations between wall thickness measurements by using US and MRI with CVD outcomes. Results The adjusted hazard ratios for coronary heart disease, stroke, and CVD associated with per standard deviation increase in intima-media thickness were 1.10, 1.08, and 1.14, respectively. The corresponding associations for mean wall thickness measured with proton-density-weighted MRI were 1.32, 1.48, and 1.37, and for mean wall thickness measured with gadolinium-enhanced MRI were 1.27, 1.58, and 1.38. When included simultaneously in the same model, MRI wall thickness, but not intima-media thickness, remained associated with outcomes. Conclusion For individuals without known cardiovascular disease at baseline, wall thickness measurements by using MRI were more consistently associated with incident cardiovascular disease, particularly stroke, than were intima-media thickness by using US. © RSNA, 2018 Online supplemental material is available for this article.