Ischemic preconditioning is a useful manipulation to reduce the undesirable effects of ischemia. The beneficial results of this phenomenon against ischemia-reperfusion have been seen in different flap models; however, all these studies have focused on primary ischemia. In this study, we investigated the effects of ischemic preconditioning on secondary ischemia in a skin flap model. We used the 6- x 3-cm-sized epigastric skin flap in 40 Wistar rats. In all animals, primary global ischemia of 2 hours was followed by 4 hours of either arterial or venous secondary ischemia 24 hours after the primary ischemia and ischemic preconditioning (IP) was tested in this protocol. Ischemic preconditioning was performed by 2 cycles of 15 minutes of repeated ischemia/reperfusion periods. The animals were allocated into 4 groups: group 1 (n = 10 animals): primary ischemia (2 hours) + secondary arterial ischemia (4 hours); group 2 (n = 10 animals): IP + primary ischemia (2 hours) + secondary arterial ischemia (4 hours); group 3 (n = 10 animals): primary ischemia (2 hours) + secondary venous ischemia (4 hours); group 4 (n = 10 animals): IP + primary ischemia (2 hours) + secondary venous ischemia (4 hours). Flap viability was assessed 1 week after the surgical procedure, and surviving flap area was recorded as a percentage of the whole flap area. Group 1 was compared with group 2, and group 3 was compared with group 4 to evaluate the effects of ischemic preconditioning against secondary arterial and venous ischemia. t test and Mann-Whitney rank sum tests were used for statistical analysis. There were statistical differences both between groups 1 and 2 and groups 3 and 4. The results revealed that ischemic preconditioning was an effective procedure to reduce the flap necrosis as a cause of secondary ischemia in skin flaps.