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The search for biomarkers that can help to establish an early diagnosis and prognosis of interstitial lung disease (ILD) is of potential interest. <i>VEGF</i> polymorphisms have been implicated in the development of several lung disorders. Consequently, we assessed, for the first time, the role of <i>VEGF</i> polymorphisms in the susceptibility and severity of ILD. A total of 436 Caucasian ILD patients (244 with idiopathic interstitial pneumonias (IIPs) and 192 with non-IIP) and 536 ethnically-matched healthy controls were genotyped for <i>VEGF</i> rs833061, rs1570360, rs2010963, rs3025020, and rs3025039 polymorphisms by TaqMan assays. Pulmonary function tests were collected from all the patients. VEGF serum levels were determined by ELISA in a subgroup of patients. No <i>VEGF</i> genotype, allele, carrier, or haplotype differences were found between ILD patients and controls as well as between IIP and non-IIP patients. However, an association of rs1570360 with IIP in women and also with lung function in IIP patients was found. None of the <i>VEGF</i> polymorphisms were associated with VEGF levels. In conclusion, our results suggest that <i>VEGF</i> does not seem to play a relevant role in ILD, although rs1570360 may influence the severity of ILD in women and a worse outcome in IIP patients.