This study evaluated the acute effect of statin administration in smokers. We conducted a prospective study to determine the acute effect (24 hours) of single-dose atorvastatin (20 mg) on brachial artery endothelial function using vascular ultrasonography (flow-mediated vasodilation [FMD]) and blood flow in normolipidemic smokers (10 men, 42 +/- 9 years of age) and healthy nonsmokers (10 men, 39 +/- 7 years of age). Atorvastatin increased brachial artery percent FMD in smokers from 4.1 +/- 1.4% to 5.7 +/- 1.7% (p <0.0005), whereas we found no significant change after atorvastatin in nonsmokers (from 5.8 +/- 1.2% to 5.9 +/- 1.2%, p = NS). The velocity time integral also showed a significant increase as percent FMD in smokers 24 hours after taking atorvastatin (from 19 +/- 11 to 25 +/- 12 cm, p <0.05), whereas no significant change occurred in nonsmokers (from 18 +/- 9 to 19 +/- 10 cm, p = NS). Baseline brachial artery diameter significantly dilated in smokers after taking atorvastatin compared with before taking atorvastatin (from 4.23 +/- 0.5 to 4.35 +/- 0.4 mm, p <0.05), but did not change in nonsmokers (from 4.26 +/- 0.6 to 4.31 +/- 0.6 mm, p = NS). In conclusion, single-dose atorvastatin restores endothelial function and increases brachial artery blood flow in normolipidemic men smokers within 24 hours. These findings suggest early benefits of statin therapy on endothelial function in smokers.