Objective Tissue ultrafiltration (TUF) is a method of reducing tissue edema by removal of interstitial fluid. Considering the deleterious effects of edema on microcirculation and tissue viability, the effect of TUF on skin flap survival was tested. Study design and setting Survival of modified McFarlane skin flaps was determined in 40 Sprague-Dawley rats. In 20 treated animals, four 5-cm ultrafiltration catheters were placed in the subdermal plane of the distal flap 24 hours after flap elevation and connected to a down-regulated vacuum manifold for 8 hours. No catheters were placed in the control group. Results Skin flap survival was improved in the experimental group (87.2 ±1.6) over the control group (76.7±2.2). Discussion TUF effectively improved skin flap survival. These results provide evidence of the causal effect of edema on tissue viability. The relative ease of use of TUF would allow cost-effective clinical application of this technique.