Conflicting reports exist regarding the influence of hyperbaric oxygen therapy on random skin flap survival. The present investigation sought to demonstrate enhanced survival of experimental random skin flaps in swine using an intensive and tapering hyperbaric oxygen therapy regimen that would have direct application in human clinical trials. Random cutaneous flaps were surgically constructed on 12 domestic pigs. Flaps were designed to obtain a predictable length of necrosis. Six pigs did not undergo hyperbaric oxygen therapy and served as surgical controls. Six pigs were subjected to an intensive tapering hyperbaric regimen within 1.5 hours of completing the surgical procedure. Treatments were administered in a research hyperbaric vessel at a depth of 2.0 atm absolute (10 m of seawater) for 90 minutes of oxygen treatment in a tapering schedule over 6 days. This was structured to provide intensive therapy initially during the period of maximum tissue trauma and ischemia. Extent of flap necrosis was assessed by tracing clear plastic templates at necropsy, then converting to square centimeters using a computer digitizer tablet. The difference in flap necrosis between groups was significant, with random flaps subjected to hyperbaric oxygen therapy demonstrating a mean 35% less necrosis than surgical controls. Skin flaps treated with hyperbaric oxygen therapy demonstrated a mean survival of 77%, with a range of 56% to 100%. This reflected a 12% improvement in mean surviving area for hyperbaric oxygen therapy flaps over untreated surgical controls. We are unaware of similar studies reporting a comparable degree of enhancement in random skin flap survival using hyperbaric oxygen therapy alone. Adjunctive hyperbaric oxygen therapy in an intensive tapering schedule significantly improved flap survival in this model. Further investigations need to determine the optimum frequency of treatments and depth necessary to attain maximum tissue viability.