Objective: To compare cardiovascular and ventilatory effects, immobilization quality and effects on tissue perfusion of a medetomidine–ketamine–midazolam combination with or without vatinoxan (MK-467), a peripherally acting α₂-adrenoceptor antagonist. Study design: Randomized, blinded, crossover study. Animals: A group of nine healthy Patagonian maras (Dolichotis patagonum). Methods: Maras were immobilized twice with: 1) medetomidine hydrochloride (0.1 mg kg^–1) + ketamine (5 mg kg^–1) + midazolam (0.1 mg kg^–1) (MKM) + saline or 2) MKM + vatinoxan hydrochloride (0.8 mg kg^–1), administered intramuscularly. Drugs were mixed in the same syringe. At 20, 30 and 40 minutes after injection, invasive blood pressure, heart rate, respiration rate, end-tidal CO₂, haemoglobin oxygen saturation, and muscle oxygenation were measured, arteriovenous oxygen content difference was calculated. Muscle tone, jaw tone, spontaneous blinking and palpebral reflex were evaluated. Times to initial effect, recumbency, initial arousal and control of the head were recorded. Paired t test, Wilcoxon matched-pairs signed rank test and analysis of variance were used to compare protocols; (p < 0.05). Results: Vatinoxan significantly reduced systolic (p = 0.0002), mean (MAP; p < 0.0001) and diastolic (p < 0.0001) arterial blood pressures between 20 and 40 minutes. MAPs at 30 minutes (mean ± standard deviation) with MKM and MKM + vatinoxan were 105 ± 12 and 71 ± 14 mmHg, respectively. Without vatinoxan, four animals were hypertensive (MAP > 120 mmHg), whereas with vatinoxan, four animals were hypotensive (MAP < 60 mmHg). Muscle and jaw tone were significantly more frequently present with MKM (both p = 0.039). Other measurements did not significantly differ between protocols. Conclusions and clinical relevance: In Patagonian maras, vatinoxan attenuated the increase in blood pressure induced by medetomidine. Muscle and jaw tone were more frequently present with MKM, indicating that quality of immobilization with vatinoxan was more profound.