OBJECTIVES: To describe the real-world clinical complications associated with recurrent venous thromboembolism (VTE) and to quantify the incremental direct all-cause and disease-related healthcare costs associated with recurrent VTE.  METHODS: An analysis of healthcare insurance claims from the Ingenix IMPACTdatabase was conducted. Between January 2004 and September 2008, subjects aged ≥18 years on the date of first recurrent VTE diagnosis requiring hospitalization (index recurrent deep vein thrombosis [DVT], pulmonary embolism [PE], or both) with ≥ 12 months of baseline observation prior to the index recurrent VTE were matched 1:1 with control VTE patients without recurrence, based on exact matching factors and propensity scores. The proportion of patients with post-thrombotic syndrome (PTS) was calculated for up to 1 year and compared between the two groups. All-cause health care and disease-related costs (thrombocytopenia, superficial venous thrombosis, venous ulcer, pulmonary hypertension, stasis dermatitis, and venous insufficiency) per patient per year (PPPY) were also calculated and compared between the two groups. RESULTS: The recurrent VTE and VTE control cohorts (8,001 subjects each) were well matched for age, gender, comorbidities, VTE risk factors distributions, and baseline healthcare costs. The risk of PTS was 18.1% for the recurrent VTE cohort and 6.8% for the no recurrent VTE cohort (risk ratio: 2.7 [2.4 - 2.9]). Patients with recurrent VTE had significantly higher average PPPY all-cause costs compared to control patients (mean: $86,744 versus $37,525, cost difference=$49,219; 95% CI=46,253–51,989).  Corresponding disease-related health care costs PPPY were also significantly higher for the recurrent VTE group (mean $11,120 versus $1,262, cost difference=$9,858, 95% CI=$9,081-$10,476) and represented 20.0% ($9,858 of $49,219) of the all-cause cost difference between the two groups.   CONCLUSIONS: In this large matched-cohort study, recurrent VTE patients had a significantly higher risk of PTS compared to VTE control patients and were also associated with a significant health care cost burden.