Unnecessary and excessive fluid therapy increases the risk of adverse effects such as pulmonary edema. To prevent this, a mini-fluid challenge (MFC) has been utilized to predict whether fluid therapy will improve circulatory dynamics in human intensive care medicine. The study described here investigated whether MFC is also efficacious in pigs. Thirty-two domestic pigs anesthetized and maintained under mechanical ventilation were treated with successive IV fluid administrations of 2, 1, 1, and 2 mL/kg over a 10-min period for a total dose of 6 mL/kg of Ringer lactate. The percentage increase in mean arterial pressure (MAP) at 2, 3, and 4 mL/kg of cumulative fluid administration was examined to determine whether responders could be identified that would benefit hemodynamically from higher doses of fluids. For the purposes of this study, a 10% increase or more in MAP after 6 mL/kg of fluid administration defined responders, and an increase of less than 10% in MAP was used to define nonresponders. The percentage increase in MAP at 2, 3, and 4 mL/kg fluid administration was evaluated to determine whether this could predict responder status. Eleven of the 32 animals were determined to be responders. Responder status was predicted with high accuracy by the administration of 3 mL/kg (AUC = 0.98) and was moderately predicted with administration of 2 mL/kg (AUC = 0.80), as well as pulse pressure variation (AUC = 0.75). Thus, MFC may be helpful to maintain tissue perfusion in pigs through the use of managed fluid therapy.