Medetomidine is an α-2 adrenoceptor agonist commonly combined with ketamine for immobilization of nondomestic mammals. However, it may cause some remarkable adverse effects such as bradycardia, hypertension, and hypoxemia. Vatinoxan (previously called MK-467 and L-659,066) is an α-2 adrenoceptor antagonist that affects mostly the peripheral receptors due to its minimal ability to cross the blood–brain barrier. Therefore it alleviates the peripheral cardiovascular and pulmonary effects of medetomidine while sedation is maintained. In this study, the hypothesis was that vatinoxan would dose-dependently alleviate medetomidineinduced bradycardia, hypertension, and hypoxemia when administered intravenously (IV) after medetomidine and ketamine were administered intramuscularly (IM) to markhors (Capra falconeri heptneri), without impairing the immobilization. Various doses of vatinoxan were studied. In this prospective, randomized, assessor-blinded, clinical crossover study, eight markhors were immobilized two times (16 paired immobilizations altogether) with medetomidine (80 µg/kg) and ketamine (1.5 mg/kg), according to the estimated weight, IM in the same dart. Approximately 19 min later, vatinoxan (117-297 µg/kg) or saline placebo was injected IV. Atipamezole was used as a reversal agent. Pulse and respiratory rates, indirect blood pressures, arterial oxygen saturation, and body temperature were measured and blood samples collected. In general, vatinoxan alleviated the hypertension induced by medetomidine without affecting the quality of immobilization. The dose of vatinoxan correlated significantly with the reduction in arterial blood pressure. Vatinoxan showed potential to enhance cardiovascular function in captive nondomestic small ruminants immobilized with medetomidine–ketamine.