OBJECTIVES: To understand real-world impacts of venous leg ulcer (VLU) on direct medical costs and productivity in the US and the UK. METHODS: This prospective, observational, multi-center study enrolled 112 patients with VLU (US: 76 and UK: 36).  Patients were followed for 12 weeks or until all their ulcers healed in 2007 and 2008. Data were gathered on health care resources used at the study site as well as outside the study site (using patient diaries). Standard national data sources were used to assign unit costs to the resources used. The mean direct medical cost was estimated from the US payer, US provider, and UK National Health Service (NHS) perspectives separately and stratified by ulcer healing status.  Work productivity loss was captured weekly by the Work Productivity and Activity Impairment (WPAI) Questionnaire [1] specific for VLU. RESULTS: The mean direct medical cost of treating VLU during the study period was estimated to be $1772 per patient for US payers, $1294 for US providers, and £1502 in the UK. The largest direct medical cost component was for professional services, or labor (approximately 70%), followed by dressing, compression bandages, and medications.  Patients who had at least one ulcer not healed at the end of study had higher mean costs compared to those patients who had all ulcers healed ($2250 vs. $1012 from the US payer perspective, $1625 vs. $862 from the US provider perspective, and £1770 vs. £965 from the UK NHS perspective).  Over the 12-week study duration, more reductions in work productivity loss and activity impairment were found in the healed group vs. the non-healed group. CONCLUSIONS: VLU imposes significant medical costs and work productivity losses. Since the cost of professional services is the main cost driver in the treatment of VLU, new technologies that reduce the professional labor time could significantly reduce the economic burden of venous leg ulcer.  [1] Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of work productivity and activity impairment instrument. Pharmacoeconomics 1993;4:353-65.