The objectives of this research was to study the sedation and anaesthetic characteristics of intravenous xylazine and dexmedetomidine combined with ketamine-midazolam-isoflurane and to evaluate the cardiopulmonary effects during the anaesthetic period. Stallions were premedicated with xylazine (1.1 mg/kg IV) in Group 1 and dexmedetomidine (3.5 µg/kg IV) in Group 2. Sedation quality was evaluated and scored. General anaesthesia was achieved with ketamine (2.2 mg/kg IV) and midazolam (0.1 mg/kg IV) in both groups and anaesthesia was maintained with isoflurane inhalant in fresh oxygen gas flow (6-8 L/min). All the stallions underwent an orchiectomy by the half- closed method. Cardiovascular variables and pulmonary variables were recorded using multi gas vital sign monitor. Anaesthetic parameters, reflex status and quality of muscle relaxation were assessed. After the surgical procedure, recovery was monitored and scored on 6 point scale. Sedation score and quality was clinically better in Group 2. The difference in cardiopulmonary variables was statistically not significant. However, statistically significant changes were noticed between two groups with regard to some blood gas values during the intra-operative and at 15 min post anaesthetic period. Quality of muscle relaxation was better in group 2. Recovery was not significant. Overall quality of anaesthesia and recovery was almost similar in both the groups. In conclusion, both drug combinations produced satisfactory results for castration in the horses studied. In this study, dexmedetomidine at 3.5 µg/kg and xylazine at 1.1 mg/kg sedative doses did not result in much significant changes compared to one other.