Abstract Objective To assess the usefulness of glycopyrrolate (GLY) in preventing the decrease in cardiac index (Cl) usually caused by xylazine (XYL)/ketamine (KET)-induced anesthesia in horses. Animals 6 healthy horses. Procedure Horses were treated with saline solution or 2.5 μg of GLY/kg of body weight, administered IV. 15 minutes later, XYL (1 mg/kg) was administered IV followed 5 minutes later by KET (2 mg/kg) administration. The horses were positioned in left lateral recumbency, insufflated with 15 L of oxygen/min, and maintained for 30 minutes on the infusion of 0.05 mg of XYL and 0.1 mg of KET/kg/min. Mean, systolic, and diastolic arterial blood pressures, mean pulmonary arterial and central venous pressures, heart rate, Cl, and arterial and mixed venous blood gas tensions were recorded up to 40 minutes after anesthesia induction. Intestinal motility was assessed by auscultation of 4 abdominal quadrants for 24 hours after induction. Data were analyzed by Wilcoxon's rank-sum test for nonparametric observations, and by ANOVA for repeated measures and Scheffe's test for continuous parametric variables. Results Horses given GLY had significantly higher heart rate; mean, systolic, and diastolic arterial blood pressures; Cl; oxygen delivery; and mixed venous oxygen tensions, with significantly less tissue oxygen extraction, compared with saline-treated horses. Both groups had complete loss of intestinal motility associated with general anesthesia. Conclusions GLY significantly reduced the cardiovascular dysfunction attributable to general anesthesia with XYL and KET. The return of intestinal motility was delayed by 3 to 6 hours without causing any serious side effects. (Am J Vet Res 1996;57:1762–1770)