Single-nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene may have clinical implications. The aim of this study was to investigate the possible predictive value of the VEGF-A SNPs, in patients with metastatic colorectal cancer (mCRC) treated with first-line capecitabine and oxaliplatin (XELOX). The study included 72 patients with mCRC. Genomic DNA was isolated from whole blood, and SNPs were analyzed by PCR. SNPs were correlated with response and progression-free survival (PFS). Haplotypes were estimated using the PHASE program. Response was observed in 21% of the patients with the -2578 CA genotype compared with 59% of the patients with CC+AA, P=0.002, in 26% of the patients with the -460 CT genotype compared with 57% with CC+TT, P=0.01, and in 27% of the patients with the +405 GC genotype compared with 54% with GG+CC, P=0.02. Two SNPs were significantly related to PFS. A haplotype with a significant relationship to response was identified. The results demonstrated obvious relationships between genetic variations in the VEGF-A gene and response to first-line XELOX in patients with mCRC, which translated to a significant difference in PFS. The results call for validation in a larger cohort of patients.