Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a significant phenotypic variability in progression of the disease. Vascular endothelial growth factor (VEGF) has been reported to play a major role in renal pathophysiology. The aim of the present case-control study was to evaluate the association of two promoter polymorphisms (-2578C>A and -1154G>A) of VEGF gene and ADPKD. Genotyping was carried out in 123 ADPKD patients and 100 healthy controls, using a polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The genotype, allele and haplotype frequencies of these two polymorphisms in ADPKD patients were compared with those in controls, as well as in patients with early and advanced chronic kidney disease (CKD) stages, using Chi-square (χ2) test. The distribution frequency of CC, CA and AA genotypes of -2578C>A polymorphism differed significantly between patients and controls (0.31, 0.63 and 0.06 vs 0.37, 0.44 and 0.19, respectively (P= 0.003)), but not significantly different genotype distribution was observed for the -1154G>A polymorphism. The A allele of -2578C>A and G allele of -1154G>A, were significantly more present in the controls as compared to the patients, and may provide protection for CKD under recessive (OR, 3.73; 95% CI, 1.45-9.62; P= 0.0042), and dominant (OR, 0.55; 95%CI, 0.31-0.98; P= 0.041) models. The [A;G] haplotype was more frequently present in controls (18%) than in cases (8%), (OR 0.398; 95% CI 0.22-0.71; P= 0.002). These results suggest that the two promoter polymorphisms of VEGF may modify the disease risk in ADPKD patients from North India.