Acquired resistance to activated protein C has been reported during oral contraception and pregnancy. Its thrombogenic potential was studied in 41 neurosurgical patients who were enrolled in the placebo group of a thromboprophylaxis trial. Normalized activated protein C sensitivity ratio (nAPC-SR), clotting activity of factors V and VIII, and levels of protein C antigen were measured prior to and at days 3 and 7 after surgery. Bilateral venography was done in all patients at days 8-10 to demonstrate deep vein thrombosis. A lowered nAPC-SR was found in 76% (baseline), 80% (day 3), and 88% (day 7) of patients. It was inversely related to factor VIII clotting activity (p = .0003) and protein C antigen, (p = .02). Deep vein thrombosis was demonstrated in 30% of patients with a normal nAPC-SR and in 23% of patients with a lowered nAPC-SR. Pulmonary embolism was not observed. Multivariate analysis did not identify a lowered nAPC-SR as a thrombotic risk factor, in contrast with gender (women, p = .02) and Quetelet index (> or = 25 kg/m2, p = .006). Our data provide no evidence that acquired activated protein C resistance, frequently found in neurosurgical patients, contributes to their high risk of postoperative deep vein thrombosis.