Human kininogen domain 3 (HK-D3) polypeptides and biologically active variants and derivatives of HK-D3 are anti-angiogenic. These molecules are used to inhibit angiogenesis or treat a disease or condition in which angiogenesis is pathogenic. Because of their anti-angiogenic potential, these molecules compounds are useful in the treatment of cancer by inhibiting or reversing the growth of primary or metastatic tumors.