Objective- To compare the time of onset, duration of action and the extent of analgesia produced by a lidocaine/xylazine combination with that produced by lidocaine and xylazine alone after injection into the caudal extradural space of the Iranian river buffalo. Design- Observer-blind prospective descriptive trial, Latin square design. Animals- Eleven adult (aged over 2 years) female non-gravid healthy Iranian river buffaloes (Bubalus bubalis), weighing from 450 to 650 kg. Procedure- Caudal extradural analgesia was achieved in buffaloes on 3 occasions at 14-day intervals by injection of 2% lidocaine (L; 0.22 mg kg-1 ), 2% xylazine (X; 0.05 mg kg-1 ), and a combination of 2% lidocaine(0.22 mg kg-1 ) / 2% xylazine (LX; 0.05 mg kg-1 ) in a Latin square design. Analgesia was determined by the lack of response to pin-prick and haemostat pressure in the skin of the caudal areas. Results- Onset of analgesia for X was significantly longer (5.5 ± 0.7 minutes) than that for L or LX. Duration of analgesia was significantly longer for LX (172.3 ± 17.7 minutes) than for either drug used alone (lidocaine, 79.5 ± 5.7 minutes; xylazine, 136.4±11.4 minutes). In X and LX groups, the level of analgesia ascended to thoracic segments; however, in lidocaine-treated buffaloes thighs, flank, and udders remained sensitive. In all buffaloes, xylazine, administered either alone or with lidocaine, induced mild to moderate ataxia. Conclusions – The LX combination provided a more rapid onset, a longer duration of analgesia, and a more cranial spread of analgesic effect compared with either drug alone. Clinical relevance: The LX combination may offer a fast and long lasting anesthesia/analgesia to perform obstetrical and surgical procedures without the need for re- injection.