The U.S.-wide prevalence of venous thromboembolism (VTE) is unclear, with reported VTE incidence estimates varying widely. This retrospective analysis of healthcare claims data from patients in the Thomson Reuters national MarketScan(®) Commercial and Medicare databases (January 2002-December 2006) estimates the U.S. prevalence of VTE, and assesses associated temporal trends. Of 12.7 million study-eligible patients, 200,007 had VTE. The overall prevalence of VTE (cases per 100,000) increased by 33.1% during the study period: from 317 in 2002 to 422 in 2006. VTE was more prevalent in women than men throughout the study. The annual prevalence of VTE increased with age: 1,382 in patients ≥65 years versus 231 in patients <65 (2006 data). The number of U.S. adults with VTE is projected to more than double from 0.95 million in 2006 to 1.82 million in 2050. These data confirm that VTE remains a major healthcare burden in the US, particularly among the elderly, and highlight a continuing increase in prevalence of the disease. Greater efforts are required to improve awareness of VTE and improve standards of VTE prevention in healthcare organizations.