Background: In venous malformations (VM) the altered blood flow pattern due to a dysfunctional endothelium generates a prothrombotic state that will lead to localized intravascular coagulopathy (LIC), noticed by D-dimer elevation, pain, swelling and functional limitation. Rivaroxaban treatment prevents thrombin formation, preventing the constant stimulus for angiogenesis within the VM, stabilizing its growth, avoiding pain and allowing the antiangiogenic action of rapamycin to be effective. Procedure: A retrospective chart review was performed , including pediatric patients with extensive intramuscular VM in lower limbs suffering continuous pain and functional impotence. We evaluated laboratory values of D-dimer, pre and post-combined rivaroxaban and rapamycin treatment, VM volume assessed on magnetic resonance imaging (MRI), and clinical response defined by disappeared pain. Results: Five patients were included in the study. All of them had been multi-treated with sclerosis, endovascular laser and pressotherapy. Pain control was barely achieved by using anti-inflammatory drugs and low molecular weight heparin (LMWH). Rapamycin therapy slightly decreases D-dimer values, but they barely improved the symptoms. Despite all efforts, the clinical evolution was unsatisfactory worsen by limiting their normal life activity. We decided to initiate rivaroxaban therapy as a compassionate use regime with prophylactic dosage (10 mg/daily). All patients presented normal D-dimer levels after treatment, no side effects or bleeding episodes have been observed, the malformation volume was significantly reduced and patients were recovered without recurring pain episodes or functional impotence. Conclusions: This study suggests that prophylactic dosage of rivaroxaban in association with rapamycin improves coagulopathy in intramuscular venous malformations by reducing D-dimer levels, disappearing pain and reducing malformation volume.