OBJECTIVES: The prevalence of VTE and its associated morbidity and mortality is difficult to assess. This is due to its often silent nature, difficulty of diagnosis and follow up, and lack of routine post-mortems. This is thought to result in marked underestimates of its true burden. VITAE is the first large-scale study that aims to determine the burden of VTE at a European level. METHODS: A modified incidence-based epidemiological model was developed to estimate the number of VTE events and deaths taking into consideration recurrence and complications. Separate models were constructed for France, UK, Germany, Italy, Sweden and Spain; the total number VTE events were extrapolated for the EU. These comprehensive models were populated with published literature when available and expert observation when necessary. Both community-acquired and hospital-acquired events were derived. The former were based on a large European epidemiological study (EPI-GETBO) and the latter were derived using a hospital episode statistics database in conjunction with a “bottom-up” approach. RESULTS: The total annual burden of VTE across the EU was estimated to be 641,275 symptomatic deep-vein thromboses (DVT), and 382,550 pulmonary emboli (PE). VTE-related deaths were estimated at 478,500. Of these deaths, 34,450 (7%) patients had been diagnosed with VTE and treated, 163,050 (34%) were estimated to be sudden fatal PE and 281,000 (59%) followed undetected PE. These findings were tested using probabilistic sensitivity analyses. CONCLUSION: The VITAE study confirms that VTE is a major public health problem in the EU. Many of these events and deaths were sudden or due to undetected disease. Given the availability of effective VTE prophylaxis, many of these events and deaths are preventable. This is of particular importance in the medical setting where the implementation of prophylaxis remains suboptimal. Further research to estimate the impact of increased prophylaxis use is urgently needed.