Background: Tiletamine-zolazepam is a combination of dissociative anaesthetic with benzodiazepine agent. It is an injectable anaesthetic agent which is either used alone or in combination with other anaesthetic drugs. The objective of this study is to evaluate the anaesthetic effects of tiletamine-zolazepam alone and in combination with xylazine and xylazine-ketamine in dogs. Methods: Eighteen dogs irrespective of age, breed, sex and body weight (requiring various surgical corrections) were randomly divided into three groups viz., A, B and C. Atropine sulphate (0.025mg/kg SC) was administered in all the groups followed by tiletamine-zolazepam (till effect IV) in group A, xylazine (0.5 mg/kg IM) and tiletamine-zolazepam (till effect IV) in group B and xylazine (0.5 mg/kg IM), ketamine (2.5 mg/kg IV) and tiletamine-zolazepam (till effect IV) in group C. A gap of 10 minutes was kept between administration of each drug. The efficacy of the anaesthesia was evaluated by observing clinico-physiological parameters i.e. induction dose, induction time, duration of anaesthesia, sternal recumbency time, complete recovery time, jaw relaxation score, pedal reflex score, palpebral reflex score (PLR), heart rate (HR), respiration rate (RR), rectal temperature, capillary refill time (CRT), systolic arterial pressure, diastolic arterial pressure, mean arterial pressure and haemoglobin oxygen saturation. These clinico-physiological parameters were evaluated at different time intervals i.e. 0, 10, 15, 25, 35, 45, 60, 75, 90 and 105 minutes. Result: The induction dose of tiletamine-zolazepam observed in group A, B and C were 6.5, 5.5 and 4.0 mg/kg body weight, respectively on intravenous administration. Analgesia and muscle relaxation was observed slightly better in group C in comparison to group A and B. Heart rate increased and respiration rate decreased post induction in all three groups. Tiletamine-zolazepam with its fast and smooth induction, intermediate duration of action, excellent muscle relaxation and good compatibility with xylazine and ketamine, was found to be an effective general anaesthetic either alone or in combination. Group C with xylazine, ketamine and tiletamine-zolazepam combination required significantly lower induction dose and provided longer duration of anaesthesia in comparison to group A and B.Combining xylazine and xylazine-ketamine as pre-medicants at sub-anaesthetic doses reduced the induction dose of tiletamine-zolazepam, provided longer duration of anaesthesia, good muscle relaxation and stable physiological parameters.