The aims of this study were to determine if a propofol constant rate infusion (CRI) in Speke's gazelle, Gazella spekei, would serve as an effective alternative maintenance anesthetic, result in shorter recovery times, and improve anesthetic recovery quality when compared with isoflurane. Eight adult gazelle were enrolled in this complete crossover study with a minimum 3-wk washout period. All gazelle were induced with 10 mg/kg intravenous propofol and maintained with either propofol CRI (0.4 mg/kg/min) or isoflurane (1–3%) for 45 min. Animals were monitored for anesthetic depth and physiologic variables including heart and respiratory rates, oxygen saturation, end-tidal carbon dioxide, indirect blood pressure, and temperature every 5 min. Blood gas samples were analyzed within the first 10 min following anesthetic induction and within the last 10 min of anesthesia. Recovery times were recorded. Recovery quality was classified by a residual ataxia grading scale. Seven gazelle completed the study by undergoing both anesthetic treatments; one female (12 yr old) developed complications 2 days after isoflurane anesthesia, consisting of seizures, azotemia, leukocytosis, hypocalcemia, and hypomagnesemia but was treated successfully. Propofol anesthesia resulted in lower respiratory rates compared with isoflurane and a decrease in respiratory rate over time. Propofol CRI maintained blood pressure values closer to physiologically normal ranges compared with isoflurane for 45 min of anesthesia. Recovery times were comparable between propofol and isoflurane treatments. While individuals receiving propofol had higher residual ataxia scores compared with individuals receiving isoflurane, differences were not clinically important. This study demonstrated that propofol CRI (0.4 mg/kg/min) is an effective maintenance anesthetic agent in healthy adult Speke's gazelle for noninvasive procedures with endotracheal intubation and intermittent positive pressure ventilation.