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Objective— To investigate whether several different measures of carotid intima-media thickness (IMT) progression are associated with subsequent vascular events and whether such associations are independent of baseline carotid atherosclerotic profile and Framingham risk factors. Approach and Results— A longitudinal cohort study (the Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population study) was performed in 7 centers in 5 European countries (Finland, France, Italy, the Netherlands, and Sweden). Three thousand four hundred eighty-two subjects (median age 64.1 years; 47.8% men) with ≥3 vascular risk factors were recruited and monitored for a postprogression median follow-up of 21.5 months, during which time 129 subjects experienced a first vascular event (incidence of 20.4 per 1000 person-years). The 15th month progression of mean and maximum carotid IMT of the left and right common carotids, bifurcations, internal carotid arteries, and their composite measures, as well as the fastest IMT max progression (Fastest-IMT max-progr ) detected in the whole carotid tree regardless of location, were used in statistical analyses. All carotid IMT measures showed significant progression during the first 15 months ( P max-progr was significantly associated with the risk of subsequent vascular events. The Fastest-IMT max-progr association persisted after Bonferroni correction for multiple comparisons and after adjustments for Framingham risk factors and pharmacological treatments (all P P =0.003). Conclusions— The Fastest-IMT max-progr , a novel approach to assess carotid IMT progression, identifies focal increases of carotid IMT and, in contrast to other progression variables, is associated with cardiovascular risk.