Random-pattern flap transfer is one of the most popular procedures for covering soft tissue defects. Ischemic preconditioning is a protective endogenous mechanism capable of reducing ischemia-reperfusion injury, and it has been shown that preconditioning by proximal pedicle clamping can improve flap survival. However, the method is not suitable for random-pattern flap transfer in the clinical setting. The present study evaluates the effect of ischemic preconditioning of Wistar rat hind limbs upon dorsal random-pattern skin flap survival. Ischemic preconditioning was induced by ischemia of the right hind limb during 10 min, followed by 30 min of reperfusion. Thirty-two animals were divided in two groups. In group 1, a dorsal random-pattern skin flap measuring 2 × 7 cm was raised immediately after the induction of ischemic preconditioning. The animals in group 2 (controls) received the same treatment, but without ischemic preconditioning. The survival area was defined as the surface of the viable tissue (square centimeter) on the fifth postoperative day. The average survival area was 6.57 ± 0.18 cm2 in group 1 and 4.44 ± 0.21 cm2 in group 2. All preconditioned animals presented significantly higher flap survival areas than the controls (p ≤ 0.01, Student’s t test). Our findings show that flap necrosis was reduced by the induction of ischemic preconditioning in a body area distant from the flap harvest site, and that ischemic preconditioning has a systemic protective effect on dorsal random-pattern skin flaps and increase survival. A better understanding of the mechanism involved may improve the clinical condition of patients requiring random-pattern skin flap transfer, especially in high-risk groups.