Angiogenesis plays a key role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is one of the major angiogenic factors. In the study we have evaluated the efficiency of antisense oligodeoxynucleotides (AS-ODN) against VEGF selected from computational prediction of VEGF mRNA structure. Twenty-five different AS-ODN in two different tumor cell lines were investigated. Treatment of cell line EJ28 by VEGF723 resulted in a 83.5% suppression of VEGF protein when compared with control-ODN. Three further AS-ODN reduced VEGF protein more than 45% in comparison to control-ODN. This was caused by an antisense-specific downregulation of the VEGF transcript determined by real-time PCR. Furthermore, antisense-mediated inhibition of VEGF was associated by a reduced cell viability. In MCF-7 cells VEGF protein was inhibited more than 45% by two AS-ODN. In conclusion, we found that computational prediction of potential single strand mRNA motifs is a well suitable method to elect effective AS-ODN.