This study was conducted to evaluate the anesthetic quality produced by ketamine hydrochloride (K) (3 mg/kg, I.V.) and ketamine–propofol (K-P) mixture (2 mg/kg-1 mg/kg, I.V., respectively) in six donkeys premedicated with xylazine (X), (1 mg/kg, I.V.). Each donkey was anesthetized one time with each dose of (K) and (K-P), five minutes after (X) administration, in random order at (1) week intervals. The anesthetic parameters; induction and sleeping time, abolishment of the swallowing reflex, recumbencey period, cardiopulmonary responses, were qualitatively and quantitatively assessed. The results revealed presence of significant difference (p< 0.05) in the induction and sleeping time between (K) and (K-P) protocols. Neither the swallowing reflex, nor recumbency period represented statistical difference between (K) and (K-P) protocols. But clinically, anesthesia with (K-P) produced shorter and smoother recovery to recumbency than with (K), and the swallowing reflex was abolished while persisted with (K) anesthesia. The excellent anesthesia produced with K-P was characterized by smooth, calm, gradual and free of excitement induction (23.75±1.75 sec), good narcosis (22.50±3.57 minutes) and muscle relaxation. The swallowing reflex was abolished for (15.75±5.61 minutes). The recumbency period was characteristically smooth and featured by its rapidness (10.50±2.62 minutes). While on the other hand, induction of anesthesia with (K) protocol was characterized by rough, slow and excitement (56.25±8.44 sec), muscle rigidity, and persistence of the swallowing reflex (not disappeared or slightly disappeared). The shorter sleeping time (10.5±0.95 minutes) and the longer recumbencey (14.75±2.28 minutes) periods that was associated with violent convulsion and excitement, were clinically an obvious associate with (K) anesthesia. The intubations with (K-P) anesthetic protocol was easily performed, but was difficult or failed during (K) anesthesia.In conclusion, anesthesia with (K-P) protocol produced an excellent anesthetic mixture for induction of general anesthesia in donkeys, and up to our knowledge this the first report on the use of this mixture for total intravenous anesthesia in donkeys.