Systemic thromboembolism is an extraintestinal manifestation of inflammatory bowel disease (IBD), and an important cause of patient morbidity and mortality. The underlying basis for the hypercoagulable state in IBD is complex, and involves altered activity of all three components that govern hemostasis: platelets, fibrinolysis, and the coagulation cascade. Currently, there are no distinct guidelines for treating or preventing thromboembolic (TE) events in IBD patients compared with the general population. However, the prothrombotic state in IBD stems, at least in part, from several modifiable factors, such as hyperhomocysteinemia and an active inflammatory state. In this review we summarize the mechanisms that favor thrombosis in IBD, and the principles that need to be applied for the primary and secondary prevention of TE in this selected group of patients.