This study was performed to compare the effect of five mixtures of anesthetic protocols in thirty adult domestic ducks of local breed. The birds were randomly divided into five groups; six ducks for each group. In group1; a combination of medetomidine and ketamine (M-K), (100 µg and 20 mg/kg) drugs were used. While in group 2; a combination of xylazine and ketamine (X-K), (5 mg and 20 mg/kg) were used. For group 3; a combination of acepromazine and ketamine (Acp-K), (2 mg and 20 mg/kg) were used, and in group 4 and 5, combinations of xylazine-ketamine-diazepam (X-K-D) (5 mg; 20 mg and 5 mg/kg), xylazine-ketamine and acepromazine (X-K-Acp), (5 mg; 20 mg and 2 mg/kg), respectively were used. All the used drugs combinations were given via intramuscular route at the pectoral muscle. The time onset of loss of righting reflex was (2.6±0.5 mins), (1.6±0.5 mins), (1.1±0.3 mins), (1.0±0.1 mins) and (1.8±0.3 mins), respectively for a mean duration of time (51.3±7.5 mins), (55.0±2.0 mins), (48.8±7.5 mins), (56.3±4.3 mins) and (53.8±3.8 mins), respectively. While, the sedative effect started within (1.5±0.3 mins), (1.3±0.3 mins), (0.6±0.2 mins), (0.8±0.1 mins) and (1.3±0.3 mins), respectively. All the anesthetic combinations varied in producing proper anesthesia in the experimental ducks. The palpebral reflex was not abolished, and the eyes remained opened throughout the course of anesthesia with almost all the anesthetic combinations. Additional disadvantages accompanied administration of all 5 combinations were; persistent pedal movement, during the whole course of anesthesia. Muscle relaxation in the anesthetized birds in all 5 groups was poor, as seen clinically by the twisted necks and the contracted pedaled legs. A statistical difference (p >0.05) was found in the onset of loss of righting reflex between group 1 (2.6±0.5), compared to group 3 (1.1±0.3) and group 4 (1.0±0.1). The combination of M-K (group 1), produced good analgesia that was found to be significantly better than with the other combinations. Variable differences at respiratory rate indices at the scheduled time were found between treatment groups. But, the respiratory rate of the birds in all anesthetic protocol groups was significantly decreased from the corresponding base line values (time 0), except in K-X-D combination (group 4), in which the decrease was only at 30 minutes after injection.In conclusion the domestic ducks (Anas platyhynchos) was considered as difficult patients for anesthesia by the investigated anesthetic combinations given by intramuscular route, because none of the anesthetic regimen was effective for production of adequate anesthesia and analgesia in this species of the domestic birds.