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Background Genotypes associated with venous thromboembolism (VTE) may protect against bleeding due to a hypercoagulable state. Whether the risk of major bleeding is reduced in parallel with an increasing number of prothrombotic genotypes during anticoagulant treatment in VTE remains unknown. Objectives To investigate the association between multiple prothrombotic genotypes and risk of major bleeding in patients with VTE. Methods Patients with incident VTE (n = 676) derived from the Tromsø Study were genotyped for rs6025 (F5), rs1799963