BACKGROUND AND PURPOSE: Hypertension promotes carotid intima-media thickening. We reviewed the randomized controlled trials that evaluated the effects of an antihypertensive drug versus placebo or another antihypertensive agent of a different class on carotid intima-media thickness. METHODS: We searched the PubMed and the Web of Science databases for randomized clinical trials, published in English before 2005, and included 22 trials. RESULTS: In 8 trials including 3329 patients with diabetes or coronary heart disease, antihypertensive treatment initiated with an angiotensin-converting enzyme (ACE) inhibitor, a beta-blocker, or a calcium-channel blocker (CCB), compared with placebo or no-treatment, reduced the rate of intima-media thickening by 7 microm/year (P=0.01). In 9 trials including 4564 hypertensive patients, CCBs, ACE inhibitors, an angiotensin II receptor blocker or an alpha-blocker, compared with diuretics or beta-blockers, in the presence of similar blood pressure reductions, decreased intima-media thickening by 3 microm/year (P=0.03). The overall beneficial effect of the newer over older drugs was largely attributable to the decrease of intima-media thickening by 5 microm/year (P=0.007) in 4 trials of CCBs involving 3619 patients. In 5 trials including 287 patients with hypertension or diabetes, CCBs compared with ACE inhibitors did not differentially affect blood pressure, but attenuated intima-media thickening by 23 microm/year (P=0.02). The treatment induced changes in carotid intima-media thickness correlated with the changes in lumen diameter (P=0.02), but not with the differences in achieved blood pressure (P>0.53). CONCLUSIONS: CCBs reduce carotid intima-media thickening. This mechanism might contribute to their superior protection against stroke.