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Clevidipine is an ultrashort-acting, third-generation IV dihydropyridine calcium channel blocker that exerts rapid and titratable arterial blood pressure reduction, with fast termination of effect due to metabolism by blood and tissue esterases. As an arterial-selective vasodilator, clevidipine reduces peripheral vascular resistance directly, without dilating the venous capacitance bed. In this randomized, double-blind, placebo-controlled multicenter trial we evaluated the efficacy and tolerability of clevidipine in treating preoperative hypertension.One-hundred-fifty-two patients scheduled for cardiac surgery with current or recent hypertension were randomized to receive clevidipine or placebo preoperatively. One-hundred-five patients met postrandomization entrance criteria (systolic blood pressure [SBP] ≥160 mm Hg after inserting an arterial catheter) for reduction by ≥15% from baseline in SBP. The patients thus received infusions of clevidipine (0.4–8.0 μg · kg−1 · min−1) or 20% lipid emulsion (placebo) for at least 30 min. Treatment failure was defined as failure to reduce SBP by ≥15% from baseline or discontinuance of drug for any reason.Patients treated with clevidipine demonstrated a 92.5% rate of treatment success and a significantly lower rate of treatment failure (7.5%, 4 of 53) than patients receiving placebo (82.7%, 43 of 52; P < 0.0001). Clevidipine achieved target blood pressures (SBP reduced by ≥15%) at a median of 6.0 min (95% confidence interval 6–8 min). A modest increase in heart rate from baseline occurred during clevidipine administration. Adverse events for each treatment group were similar.Clevidipine was effective in rapidly decreasing blood pressure preoperatively to targeted blood pressure levels and was well tolerated in patients scheduled for cardiac surgery.