Three adult and two subadult greater one-horned rhinoceroses (Rhinoceros unicornis) were sedated a total of nine times using two different intramuscular sedative combinations in order to compare the effectiveness of these combinations in inducing consistent standing sedation in this species. The sedation protocols compared were butorphanol tartrate (50–60 mg) and detomidine hydrochloride (20–30 mg; BD) versus butorphanol tartrate (80–120 mg) and azaperone (80–120 mg; BA). Specific doses were adjusted according to age and sex class, and based on previous experience. Parameters compared included time to achieve defined levels of sedation, time to recovery following antagonism, physiological parameters including heart rate, respiratory rate, indirect arterial blood pressure, and venous blood gas values. A hydraulic restraint chute was utilized to mechanically restrain animals during the procedures, and blood collection and ophthalmic examinations were conducted on all animals. Both protocols resulted in standing sedation for ≥22.3 ± 2.9 min or until antagonists were administered. The BD protocol resulted in deeper and more consistent sedation, compared to the BA protocol. Naltrexone hydrochloride (250–300 mg) and tolazoline hydrochloride (1,500–2,000 mg) were administered intramuscularly to antagonize protocol BD, whereas naltrexone alone (200–500 mg) was used to antagonize BA. Time to full antagonism, defined as normal mentation and ambulation following administration of antagonists, was prolonged in the BD protocol (132.3 ± 17.2 min) compared with the BA protocol (7.5 ± 2.5 min). Venous blood gas analysis did not reveal any significant blood gas deviations during sedation when compared with either conscious equine or white rhinoceros (Ceratotherium simum) venous reference ranges. In summary, both combinations resulted in adequate standing sedation for minimally invasive procedures, although BD resulted in more profound and consistent sedation.