The role of vascular endothelial growth factor (VEGF) gene polymorphisms in the prognosis of colon cancer prognosis remains unclear. We evaluated the influence of 28 single-nucleotide polymorphisms in 12 genes in the VEGF pathway on the prognosis of 347 patients with stage II-III colon cancer. We found that rs9513070 (VEGFR1) and rs1137282 (KRAS) were associated with overall survival in stage II colon cancer patients (p = 0.025 and p = 0.001, respectively). When primary tumor location was considered, rs9513070 was also associated with relapse-free and overall survival (p = 0.033 and p = 0.031, respectively) in left colon cancer patients. Additionally, rs35251833 in the ITGAV gene correlated with relapse-free survival (p = 0.032). This study provides evidence that germline polymorphisms in VEGFR1, KRAS and ITGAV genes are associated with prognosis in stages II-III colon cancer patients. As stage and tumor location are correlated with prognosis, future genetic studies should stratify colon cancer patients according to these parameters.