Anticoagulation in most patients with familial thrombophilia-hypofibrinolysis and primary osteonecrosis (ON) before hip or knee collapse relieves pain, prevents joint collapse and usually averts the need for joint replacement but is not successful in secondary ON or if started after joint collapse. Anticoagulation in Perthes disease and in ON acutely appearing in post-COVID patients, particularly when factor V Leiden is present, may be valuable as an approach to prevent the otherwise high likelihood of subsequent joint failure. Anticoagulation in primary ON with concurrent thrombophilia-hypofibrinolysis should be considered within the treatment spectrum of ON.