This study evaluated the effect of prostaglandin E2 on skin flap survival in the porcine model. Dorsal random skin flaps on hypopigmented 15- to 25-kg pigs were used. Prostaglandin E2 (10 ng/kg per minute) was infused for 2 days prior to surgery and continued during the 7-day postoperative period. Mean flap survival was 52.58%±3.62% for the control group and 68.51%±3.34% for the experimental group (P<.05). A moderate correlation existed between prostaglandin E2 serum levels and flap viability. A strong correlation was noted between red blood cell flexibility and the amount of flap survival (r=.86). As red blood cell flexibility increased, the survival percentage also increased. Although prostaglandin E2 reduced adenosine diphosphate-induced platelet aggregation from a baseline of 86.08%±8.33% to 54.61% ±17.21%, no correlation was noted between the amount of platelet aggregation and percent flap survival (r=.52). (Arch Otolaryngol Head Neck Surg. 1994;120:56-60)