BACKGROUND: Recent studies have shown lower rates of cancer following venous thromboembolism (VTE) than previously described. OBJECTIVES: To reassess the risk of cancer in patients with clinical symptoms of VTE with or without confirmed VTE. PATIENTS: We used data from OPTIMEV, a French prospective multicenter observational study of patients presenting to hospital and community vascular medicine specialists with suspected VTE. Patients with confirmed VTE (1565) and matched controls without VTE (1847) were followed for 3 years (2006-2009). The main outcome was occurrence of cancer at 3 years, and death was a censoring event. RESULTS: A total of 5.0% [4.0-6.3] of patients with VTE and 3.8% [3.0-4.9] without VTE developed cancer during follow-up. The adjusted hazard ratio (HR) was 1.2 [0.9-1.8] for patients with confirmed VTE (P=0.22). The overall standardized incidence ratio (SIR) was 1.4 [1.1-1.6] for our population, VTE+ and VTE-, compared with the general population, statistically significant (P<0.05). CONCLUSIONS: We found a lower occurrence of cancer after VTE than previously described, with no significant difference between patients whether VTE was confirmed or not. Our results (low incidence and no difference between patients VTE+ or VTE-) provide no argument in favor of an extensive screening for cancer in case of VTE.