This paper reviews pathophysiological processes occurring after contact of blood with artificial surfaces and the predominant role of platelets in the genesis of extracorporeal thrombosis. Bleeding complications are common during conventional heparin anticoagulation, and both clinical and experimental evidence suggests that the efficacy of heparin as an anticoagulant is compromised by its relative ineffectiveness towards platelets. Consequently, drugs that inhibit interaction between platelets and artificial membranes have been introduced as an alternative anticoagulant strategy. This paper reviews studies on the use of short-acting antiplatelet prostaglandins such as prostacyclin and prostaglandin E1 alone or in combination with heparin during various forms of extracorporeal circulation such as cardiopulmonary bypass, haemodialysis, continuous haemofiltration, membrane oxygenation, ventricular assist devices, and haemoperfusion. Temporary paralysis of platelet function with antiplatelet prostaglandins has been effective in controlling platelet-surface interaction and reducing bleeding complications and morbidity during and after extracorporeal circulation. By inhibiting the formation of fibrin, leukocyte and platelet-based microaggregates and cytoprotective actions, prostaglandins have been shown to prevent renal, neurologic, and pulmonary dysfunction after extracorporeal circulation. Prostaglandins were most effective in increasing the biocompatibility of extracorporeal systems when they were administered as a supplement to but not as a substitute for heparin. The use of prostaglandins alone should be reserved for patients who are resistant to heparin or heparin-induced thrombocytopenia.