With advancing age, an increasing number of healthy individuals have laboratory signs of heightened coagulation enzyme activity. Such biochemical hypercoagulability might be the basis of either the increased thrombotic tendency occurring with age or a harmless manifestation of this process. Centenarians had striking signs of heightened coagulation enzyme activity, accompanied by signs of enhanced formation of fibrin and secondary hyperfibrinolysis. Plasma concentrations of fibrinogen and factor VIII were higher than in controls, whereas other coagulation factors were not elevated. It is of interest that centenarians have a significantly higher frequency than young individuals of the high risk 4G allele of the PAI-1-675 (4G/5G) polymorphism, mutant factor V (Arg506Gln) and prothrombin gene G20210A mutation. Von Willebrand factor (VWF), a well-known independent predictor of atherothrombotic disease, was increased in centenarians, independently of the blood group, confirming the previous results of a state of hypercoagulability. The finding that the VWF cleaving proteases levels are low when VWF levels are high in centenarians could be a corollary of the previous described paradox of successful aging, adding another marker of increased risk of atherothrombosis to the scenario. Alike, high prevalence of anti-phospholipids antibodies, not associated with an anti-phospholipid syndrome has been described in centenarians. In conclusion, the data show the oldest old do not escape the state of hypercoagulability associated with aging, but that this phenomenon is compatible with health and longevity. Hence, high plasma levels of the coagulation activation markers in older populations do not necessarily mirror a high risk of arterial or venous thrombosis.