Thromboembolism is an important cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate common thrombophilic markers in patients with IBD and to search for a relation between these predisposing factors and activity of disease. Seventy-four patients with ulcerative colitis, 22 patients with Crohn's disease and 20 healthy volunteers were enrolled into the study. Plasma levels of protein C, protein S, antithrombin III and activated protein C resistance were determined in patients with IBD and healthy controls. Mean values of protein C, protein S and antithrombin III were significantly lower in patients with ulcerative colitis and Crohn's disease compared with the healthy control group. Patients with active ulcerative colitis had lower protein C, protein S and antithrombin III level than patients in remission (P < 0.001, P < 0.001, P < 0.001). Levels of protein C, S and antithrombin III were also decreased in patients with active Crohn's disease compared with those in remission (P < 0.05, P < 0.001, P < 0.05). Differences in all natural anticoagulant levels between patients in remission and healthy individuals in both ulcerative colitis and Crohn's disease groups were not statistically significant (P > 0.05). No significant difference was observed in activated protein C resistance (APCR) between patients with active disease, those in remission and the control group (P > 0.05). Abnormalities in natural anticoagulants are common in patients with IBD during active disease.