Cytomegalovirus (CMV) seems to contribute to the development of venous thromboembolism (VTE) in immunocompromised patients whereas literature data on the role in immunocompetent individuals are mainly limited to case reports. This study aimed to investigate if cytomegalovirus infection contributes to the development of VTE in immunocompetent individuals. CMV-IgG and CMV-IgM antibody titres, CMV-IgG avidity and CMV-DNA were identified in samples from 166 VTE patients and from 166 healthy blood donors matched for gender and age. CMV-IgG antibodies were found more frequently in VTE patients compared to controls [57.8% vs. 44.0%; adjusted OR 1.75 (95% CI 1.13-2.70); p = 0.016]. Accordingly, median CMV-IgG titres were significantly higher in the case group (89.4 vs. 1.8 AU/ml; p = 0.002). Although the overall rate was low, CMV-IgM antibodies were detected more often among cases than controls. The difference was significant in patients with an unprovoked VTE event [7.4% vs. 0.6%; adjusted OR 5.26 (95% CI 1.35-20.8); p = 0.017]. CMV-IgG antibodies of almost all VTE patients (98.9%) and controls (98.6%) were found to be of high avidity. The rate of positive CMV-DNA samples was low and not different between cases and controls. With the exception of age, no association was found between CMV seropositivity and established VTE risk factors within the VTE group. CMV infection seems to play a role in the development of VTE in immunocompetent patients. Recurrent infection might be more important than acute CMV infection.