Neoangiogenesis is involved in the pathophysiology of multiple myeloma and angiopoietins possibly contribute to myeloma-induced neovascularization. Bortezomib's antineoplastic potential includes an anti-angiogenic effect. We determined serum levels of angiopoietin-1 and angiopoietin-2 with ELISA pre- and post-bortezomib administration in 35 patients with relapsed/refractory multiple myeloma. Pre-bortezomib, serum angiopoietin-1 levels did not differ in patients and in healthy individuals, while serum angiopoietin-2 levels were elevated. Corresponding serum angiopoietin-1/angiopoietin-2 ratio was reduced in patients compared with controls. After treatment, serum angiopoietin-1 levels increased, while serum angiopoietin-2 levels decreased, therefore the angiopoietin-1/angiopoietin-2 ratio increased and normalized. This increase was significant in patients who responded to treatment. In conclusion, angiopoietin-1/angiopoietin-2 ratio normalization reflected response to bortezomib.