Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention. Thus, the present study aimed to determine whether the VEGFA -2578C/A, -1154G/A and -634G/C polymorphisms confer risk or were associated with reduced risk of RA or SLE in a Mexican population. The present study included 903 women from Mexico: 405 were patients with RA, 282 had SLE and 216 were healthy individuals. The genotypes were obtained with TaqMan probes. The data obtained in the present study suggest that the VEGFA -2578C/A and -634G/C polymorphisms are not risk factors for RA or SLE; however, VEGFA -1154G/A was associated with reduced risk in women with RA (odds ratio=0.6, pc =0.0051) but not with SLE (odds ratio=0.7, pc =0.13). The present study is the first to document an association between VEGFA -1154G/A and reduced risk in women with RA but not with SLE.