Whether the high incidence of thromboembolic events in nephrotic patients with membranous nephropathy justifies prophylactic administration of oral anticoagulants remains controversial. We used a Markov-based decision analysis model, explicitly considering the consequences of recurrent embolic and bleeding events to quantify the risk-benefit trade-offs of: (1) prophylactic therapy, in which oral anticoagulation was started at the time of diagnosis of nephrotic syndrome (before any thromboembolic event); and (2) anticoagulant therapy, in which treatment was started after the first clinical thromboembolic event. We assumed that anticoagulant therapy was discontinued if there was remission of the nephrotic syndrome. The overall number of fatal emboli prevented by prophylactic anticoagulants exceeded the one of fatal bleeding events for all clinically meaningful ranges of the following parameters: nephrotic syndrome duration, incidence of thromboembolic events, likelihood of embolization, and mortality rates of embolic and bleeding events. For a hypothetical 50-year-old patient who remained nephrotic for 2 years, prophylactic anticoagulation yielded a gain representing 2.5 months of quality-adjusted life expectancy. We conclude that for nephrotic patients with membranous nephropathy, the benefits of prophylactic administration or oral anticoagulants outweigh the risks.