Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) play crucial roles in angiogenesis, which contributes to the development and progression of solid tumors. The aim of this study was to investigate the associations of VEGF (−2578C > A, −1154G > A, −634G > C, and 936C > T) and KDR (−604T > C and 1192G > A) polymorphisms with the development of colorectal cancer (CRC). A total of 882 participants (390 CRC patients and 492 controls) were enrolled in the study. The genotyping of VEGF and KDR polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism assay. We found that the CT and TT genotype of the 936C > T was associated with an increased risk of CRC compared with the CC genotype as the dominant model for the T allele. In addition, we also found a increased CRC risk with TC + CC genotype of KDR −604T > C compared with TT genotype in CRC patients and control subjects. Similarly, KDR 1192G > A also showed significant association between 1192G > A variants and risk of CRC. In the haplotype analyses, haplotype −2578A/−1154A/−634G/936T of VEGF polymorphisms and haplotype −604C/1192G and −604C/1192A of KDR polymorphisms were associated with an increased susceptibility of CRC. Our results suggest that the VEGF 936C > T, KDR −604T > C, and KDR 1192G > A polymorphisms may be contribute to CRC risk in the Korean population. © 2012 Wiley Periodicals, Inc.