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Clevidipine is an arterial, selective, dihydropyridine calcium channel blocker with an ultrashort half-life. In this prospective, randomized, open-label, parallel-comparison trial series, the safety and efficacy of intravenous clevidipine with nitroglycerin, sodium nitroprusside and nicardipine in hypertensive patients during cardiac surgery were compared. No differences in the incidences of myocardial infarction, stroke or renal dysfunction were observed between treatment groups. Mortality was similar between the clevidipine–nitrogylcerine- and clevidipine–nicardipine-treated groups, whereas mortality appeared to be greater in the sodium nitroprusside group compared to clevidipine (p = 0.04 in a univariant analysis). Clevidipine was significantly more effective in blood pressure control compared with nitroglycerin (p = 0.0006) or sodium nitroprusside (p = 0.003) and was associated with fewer blood pressure excursions compared with nicardipine as a predetermined blood pressure range was narrowed.