Vascular endothelial growth inhibitor (VEGI) has been associated with tumour-related vasculature in certain maligancies. However, its implication in prostate cancer remains unknown. We investigated the expression pattern and role of VEGI in prostate cancer and prostate cancer cells. The expression of VEGI was examined in human prostate tissue and prostate cancer cell lines. The biological impact of modifying the expression of VEGI in prostate cancer cells was evaluated using in vitro models. VEGI mRNA was expressed in a wide variety of human prostate cancer cell lines and most prostate specimens. VEGI protein was seen in normal prostate epithelium, but was decreased or absent in prostate cancer specimens, particularly in tumours with high Gleason scores. Moreover, forced-expression of VEGI led to a decrease in the motility and adhesion of prostate cancer cells in vitro. In contrast, knocking down VEGI in the cells resulted in an increase in motility and adhesion. Interestingly, both forced-expression and knocking down of VEGI had no bearing on growth and invasive capacity of prostate cells. In conclusion, the expression of VEGI is decreased in prostate cancer and is almost absent in tumours with high Gleason scores. Together with its inhibitory effect on cellular motility and adhesion, this suggests that VEGI functions as a negative regulator for aggressiveness during the development and progression of prostate cancer.