BACKGROUND Hypertonic saline and hydroxyethyl starches have been proposed as alternatives to isotonic crystalloids for reversal of hypovolemia in horses with colic. However, no direct comparison of these fluids has been performed in a clinical setting. HYPOTHESIS Preoperative administration of hypertonic saline or pentastarch would produce similar effects on intra operative hemodynamics in horses with colic. ANIMALS Thirty horses requiring colic surgery were enrolled in this prospective, randomized, open-label clinical trial. Inclusion criteria were owner consent, and at least 2 of 3 clinicopathologic abnormalities: packed cell volume >45%, plasma total solid concentration >8.0 g/dL, and blood lactate concentration >2.5 mM. METHODS Study horses were randomly assigned to receive 4 mL/kg hypertonic saline or pentastarch before induction of anesthesia. Hemodynamic measurements were recorded every 30 minutes during anesthesia. Cardiac output (CO) was measured by the lithium dilution method. CO and stroke volume (SV) were indexed by body weight. Data were analysed using repeated measures analysis of variance (ANOVA). Post hoc comparisons were performed using the Bonferroni test. RESULTS Cardiac index (CI) was higher in the pentastarch group compared with the hypertonic saline group from 30 to 150 minutes after induction (P = .04). SV index was higher in the pentastarch group at 30 (P = .025) and 60 minutes (P = .04). Mean arterial pressure of horses in both groups was lower at 90 minutes compared with 30 and 60 minutes. CONCLUSIONS AND CLINICAL IMPORTANCE Preoperative administration of pentastarch results in better CI than hypertonic saline, for 150 minutes after anesthetic induction. The effect of this improved global blood flow on regional perfusion or clinical outcome remains to be elucidated.