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Background The natural course of elevated factor VIII (FVIII) in patients with venous thromboembolism (VTE) and with or without inflammatory bowel disease (IBD) is not well described. Furthermore, the data on effectiveness and safety of extended anticoagulation in these patients are limited. Methods We performed a retrospective chart review of all patients with VTE, who had an elevated FVIII level (>1.5 IU/mL) during a period of 16 years. FVIII levels, duration of anticoagulation, recurrent thromboembolic events and bleeding requiring hospitalization were captured and compared between patients with and without IBD. Results Fourteen patients with IBD and 66 without IBD were followed for 8.0 years (standard deviation [SD] ±3.5) and 5.6 years (SD ±5.1), respectively. Among the 41 patients with repeat levels, FVIII remained elevated in most patients. None of the IBD patients had thromboembolic events or major bleeding during a mean of 5.6 years (SD ±5.1) of anticoagulation. Three of 5 IBD patients that stopped anticoagulation had thromboembolic events at a median of 9 months after stopping – observed event rate 12 per 100 patient-years. For the 66 non-IBD patients the event rates of thromboembolism on and off anticoagulation were 1.6 and 7.2 per 100 patient-years, respectively, and of major bleeding on anticoagulation 0.8 per 100 patient-years. Conclusion Elevated FVIII in patients with VTE is often a persistent risk factor. The cohort with VTE and elevated FVIII that we analyzed appeared to have a favorable benefit/risk ratio of extended anticoagulation.