Halothane (HAL) and isoflurane (ISO) maintenance anesthesia in 12 water buffaloes was compared on the basis of certain cardiopulmonary, hemodynamic, acid base, electrolyte, and recovery parameters. Buffaloes were randomly divided into two groups: HAL (n = 6) and ISO (n = 6), premedicated with midazolam (0.2 mg/kg) intravenously, and 5 min later, induced to anesthesia by intravenous thiopentone sodium (10 mg/kg IV, given till effect). Anesthesia was maintained with halothane or isoflurane in oxygen at a total gas flow rate of 4-6 lt/min. Results revealed that recovery with isoflurane was more rapid than halothane with a significant (p < 0.05) difference in recovery quality between two groups. Heart rate, respiration rate, rectal temperature, systolic blood pressure, diastolic blood pressure, and mean arterial pressure decreased significantly (p < 0.01) in HAL group. Values of pH(a) decreased significantly (p < 0.01) and PaCO2 increased significantly (p < 0.01) in HAL group. There were no significant (p > 0.05) differences in PaO2, HCO3, and plasma electrolytes between two groups. Values of SpO(2) decreased significantly (p < 0.05) in HAL group. Isoflurane maintenance anesthesia contributes to a shorter, safer recovery from anesthesia with maximum preservation of cardiopulmonary and hemodynamic functions along with minimal changes in acid base parameters in water buffaloes. Thus, isoflurane maintenance anesthesia is better than halothane maintenance anesthesia in water buffaloes.