Objective: A randomized, blinded clinical study was conducted to evaluate ketofol (Ketamine + Propofol combination) anesthesia in 12 entire male mongrel dogs sedated with either aceproma¬zine (ACP) or medetomidine. Materials and Methods: Group A (6) dogs were pre-medicated with ACP and Group B (6) dogs with medetomidine. Anesthesia was induced and maintained using ketofol (ketamine and propo¬fol). Routine open pre-scrotal castration was performed. Sedation score and ease of arousal were assessed and recorded. Duration and depth of anesthesia were evaluated using apnea and the absence of palpebral and pedal reflexes, attempts to stand up, and muscle tremors and post-operative pain. Simple statistics were compared using Student t-test and MannWhitney test (p < 0.05). Results: Medetomidine-sedated dogs had higher sedation scores compared to ACP-sedated dogs. Medetomidine-ketofol produced significantly (p < 0.05) longer duration of anesthesia (24.5 ± 3.1 min) compared to ACP-ketofol (10.0 ± 4.4 min). Sixty-seven percent of dogs anesthetized with ACP-ketofol required top up with ketofol to complete the castration. However, none of the Med-ketofol anesthetized dogs required top up. Med-ketofol produced a more profound depth of anes¬thesia and smoother recovery from anesthesia compared to ACP-ketofol. Med-ketofol (median score 6) attained better overall post-operative analgesia compared to ACP-ketofol (median score 7), though not statistically significant (p = 0.25). Although both protocols provided adequate anes¬thesia for castration, top up was required to complete the operation in more than half of ACP-ketofol anesthetized dogs, making Med-ketofol a better protocol. Conclusion: The study recommends the use of Med-ketofol anesthesia for castration in a dog, and post-operative analgesia to be administered with either protocol, but more so in ACP-ketofol anesthetized dogs undergoing castration. [J Adv Vet Anim Res 2019; 6(2.000): 215-221]