ObjectiveWe hypothesized that propofol can produce rapidly-reversible, dose-dependent standing sedation in horses. Study designProspective randomized, blinded, experimental trial. AnimalsTwelve healthy horses aged 12 ± 6 years (mean ± SD), weighing 565 ± 20 kg, and with an equal distribution of mares and geldings. MethodsPropofol was administered as an intravenous bolus at one of three randomized doses (0.20, 0.35 and 0.50 mg kg−1). Cardiovascular and behavioral measurements were made by a single investigator, who was blinded to treatment dose, at 3 minute intervals until subjective behavior scores returned to pre-sedation baseline values. Continuous data were analyzed over time using repeated-measures anova and noncontinuous data were analyzed using Friedman tests. ResultsThere were no significant propofol dose or temporal effects on heart rate, respiratory rate, vertical head height, or jugular venous blood gases (pHv, PvO2, PvCO2). The 0.35 mg kg−1 dose caused mild sedation lasting up to 6 minutes. The 0.50 mg kg−1 dose increased sedation depth and duration, but with increased ataxia and apparent muscle weakness. Conclusions and clinical relevanceIntravenous 0.35 mg kg−1 propofol provided brief, mild sedation in horses. Caution is warranted at higher doses due to increased risk of ataxia.