OBJECTIVES: To conduct a literature review on the economic burden of venous thromboembolism (VTE) (encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE)) and related complications. METHODS: Eligible English-language studies published post-1990 were identified from electronic databases (Medline, EMBASE and Cochrane Library: accessed December 2012) and conference proceedings with no restriction on geographical location or patient population. All costs are reported in US$ adjusted to 2013 levels. RESULTS: Twenty nine studies met eligibility criteria: United States (n=17), Canada (n=2), Australia (n=1), South America (n=1) and Europe (n=8). The estimated annual cost of VTE treatment is in excess of $2 billion in the USA and Europe and $153 million in Australia. This figure rises to $15.6–$34.8 billion in the US and to $1.78 billion in Australia on inclusion of complications, productivity loss and other societal costs. The cost of treating PE per patient ($12,567-$20,488) is higher than that of treating DVT ($2,912-$13,299). Hospitalisation is the main cost driver for VTE treatment, accounting for 56%-89% of all treatment costs. For patients with cancer, costs were 30-50% higher for those with VTE compared with those without VTE. VTE-related complications incur additional costs including: bleeding (up to $23,963 per patient with a major bleed); recurrent VTE (up to $18,122 per patient); post-thrombotic syndrome (increase of up to 75% in treatment cost); chronic thromboembolic pulmonary hypertension (up to $6,708 per patient); and heparin-induced thrombocytopenia (up to $18,779 per patient). CONCLUSIONS: Incident VTE events and related complications are associated with significant economic burden across several patient populations. Treating PE may cost up to five times more than treating DVT, with hospitalisation reported as the major cost driver of VTE treatment. Effective and convenient therapies associated with both a reduced incidence of bleeding and complications are required to further reduce the cost burden associated with VTE.