Venous thromboembolism (VTE) is a common disease with many manifestations. Despite the recent progress in VTE treatment, there remain knowledge gaps in the use of direct oral anticoagulants (DOACs) in special patient populations and in the management and outcome of anticoagulant-related bleeding. This thesis focussed on some of these needs. Part I evaluated patient characteristics related to treatment and outcome of VTE. First, we found that edoxaban, a DOAC, is an effective and safe anticoagulant for patients with extensive pulmonary embolism (PE) and evidence of right ventricular dysfunction. Second, we showed a difference between the sexes in the presenting location of a first VTE; in men a deep vein thrombosis was more often observed, in women a PE. Third, the majority of patients with an indication for anticoagulant treatment preferred a DOAC over a vitamin K antagonist (VKA) after being presented with the advantages of DOACs in a questionnaire. Part II addressed the management and outcome of anticoagulant-related bleeding. We showed that the presentation of bleeding events with DOACs was milder, but the course was comparable to bleeding with VKA. Additionally, a post-hoc analysis of two trials showed that abnormal vaginal bleeding occurs more frequently in women treated with apixaban and edoxaban than with VKA. Next, our systematic review concluded that prothrombin complex concentrate (PCC) is an effective method for VKA reversal, without increasing the risk of thromboembolic complications. Finally, our bleeding registry suggested that, until specific antidotes for DOACs become widely available, PCC might be an effective option in managing bleeding complications with DOACs.