To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment of metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. In this single-arm phase II trial, 32 patients were enrolled and they received bevacizumab 15 mg/kg IV infusion in 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, adequate organ function and had not received any radiation treatment in the last 28 days. Of the 30 patients evaluated for efficacy and toxic effect, four (two angiosarcoma and two epithelioid hemangioendothelioma; 17%) had a partial response. Fifteen patients (11 angiosarcoma and 4 epithelioid hemangioendothelioma; 50%) showed stable disease with a mean time to progression of 26 weeks. Bevacizumab was well tolerated with only one grade 4 adverse event. Expected known toxic effects of the drug were manageable. Bevacizumab is an effective and well-tolerated treatment for metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. Further phase III studies of bevacizumab in combination with other chemotherapeutic agents and/or radiation treatment are warranted.