The potential for hyperbaric oxygen therapy (HBO) to decrease the untoward effects of a secondary ischemic event was studied in the rat superficial epigastric flap model. The secondary venous ischemic flap was created by cross-clamping the vascular pedicles for 2 h. Twenty-four hours later, the flap was reelevated and the venous pedicle was occluded for 5 h. Thirty-two rats were divided into three groups. In experimental group 1, animals received HBO treatment immediately prior to the initial flap elevation and ischemia at 2 atmosphere pressures for 90 min. In experimental group 2, the rats underwent a similar course except for a second 90-min HBO course immediately prior to the secondary venous occlusion. The rats without HBO therapy were used as controls. The results showed that all control flaps were nonviable at 1 week by clinical inspection and fluorescein injection. Complete flap survival occurred in 20% of group 1 flaps and 30.8% of group 2 flaps. Partial flap survival occurred in the rest of the flaps in these two groups, with mean survival areas of 48% and 55%, respectively. In conclusion, HBO treatments significantly increase the survival of flaps subjected to a secondary ischemia, even if administered before the primary ischemia. Administering HBO prior to secondary venous ischemia was marginal, which may be due to the effect of O(2) given by HBO not lasting longer than 5 h.