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Introduction Idiopathic venous thromboembolism (VTE) is associated with the risk of cancer but the risk factors for cancer development in such patients are still uncertain. Aim To assess risk factors for the development of cancer after a standard course of anticoagulation in patients with first episode of idiopathic VTE. Materials and Methods Subjects were enrolled in the three large prospective multicentre studies: PROLONG (NEJM 2006) PROLONG II (Blood 2010) and DULCIS (Blood 2014). Women whose index event was hormone related were excluded from the analysis. The development of cancer was recorded during a 2-year follow-up. Results 1,805 patients were enrolled (M/F: 510/453), mean age: 62, median: 67; range:18-87 years). Cancer developed in 55 patients (3% ; 1.7% pt-years) of whom 15 (2.0%; 1.1 % pt-years) had PE with or without DVT and 40 (3.8%; 2.1% pt-years) had DVT without PE (p = 0.03). The development of cancer was associated with DVT without PE (HR:1.8; 95% CI: 1.1-3.3) and age > 65 (HR: 2.5; 95%: 1.3-4.9). Among patients with DVT, with or without PE, the development of cancer was associated with the presence of residual vein obstruction > 4 mm (RVO) at compression ultrasound (HR: 1.8, 95% CI: 1.1-3.3) and age > 65 (HR: 2.8; 95% CI: 1.3-6.2). Conclusions Age > 65 years, DVT without PE and the presence of RVO are significantly associated with the risk of developing cancer after a first episode of idiopathic VTE over a two-year follow-up. [ABSTRACT FROM AUTHOR]