Prediction of recurrence in patients with unprovoked venous thromboembolism (VTE) remains a challenge. Studies of atherosclerosis suggest a protective role of transforming growth factor (TGF)-β. However, the role of TGF-β has not been studied in VTE. The aim of this study was to investigate TGF-β as a predictive marker of recurrent VTE in patients with a first episode of unprovoked VTE. Patients in the Malmö Thrombophilia Study (MATS) were followed after the discontinuation of anticoagulant treatment until the diagnosis of recurrent VTE or the end of the study in December 2008 (mean ± SD 38.5 months ± 27). Among patients with a first episode of unprovoked VTE, we identified 42 patients with recurrent VTE during the follow-up period. Two age- and sex-matched control subjects without recurrent VTE were selected for each patient (n = 84). Plasma levels of the three isoforms of TGF-β (TGF-β1, TGF-β2 and TGF-β3) were quantified simultaneously by TGF-β 3-plex immunoassay. Compared to controls, plasma levels of TGF-β1 and TGF-β2 were significantly lower in patients with recurrent VTE (p < 0.05), whereas no difference was found for TGF-β3. In a multivariate Cox regression analyses, adjusted for inherited thrombophilia, age, sex and BMI, low levels of TGF-β1 [hazard ratio (HR) = 2.2, 95 % confidence interval (CI) 1.1-4.3; p = 0.02] and TGF-β2 (HR = 2.4, 95 % CI 1.2-4.7; p = 0.01) were independently associated with a higher risk of recurrent VTE. We propose TGF-β1 and TGF-β2 as potential predictive markers for recurrence in patients with unprovoked VTE.