The alpha-adrenergic agonist oxymetazoline was compared to cocaine and to lidocaine with epinephrine with respect to prevention of epistaxis on nasotracheal intubation. The nares of three groups of 14 patients each were topically pretreated with 4% lidocaine with 1:100,000 epinephrine (group 1), 10% cocaine (group 2), or 0.05% oxymetazoline (group 3) prior to nasotracheal intubation. After intubation, epistaxis was estimated on a scale of 0 to 3, with 0 indicating no bleeding, 1 representing blood on the nasotracheal tube only, 2 indicating blood pooling in the pharynx, and 3 representing blood in the pharynx sufficient to impede intubation. Only 29% of the patients in group 1 displayed no bleeding, whereas 57% of those in group 2 and 86% of those in group 3 had no bleeding. Nonparametric analysis showed a statistically significant difference (p less than 0.013) between oxymetazoline and lidocaine with epinephrine. In addition, heart rate (HR) and blood pressure (BP) were examined prior to administration of the medications; at 5 minutes, 10 minutes, and 15 minutes after administration of the medications; and after intubation. No significant differences were noted (p greater than 0.05) between the medications except for a slightly higher systolic BP for cocaine than for lidocaine with epinephrine at 15 minutes. The results of this double-blind, randomized trial demonstrate that the alpha-adrenergic agonist oxymetazoline is as effective as cocaine, and more effective than lidocaine with epinephrine, for the prevention of epistaxis associated with nasotracheal intubation.