A variety of studies has linked vasoactive intestinal peptide (VIP) to idiopathic pulmonary arterial hypertension (IPAH). In this study, we investigated the correlation between VIP gene variants and IPAH in Chinese population. A total of 81 consecutive unrelated patients diagnosed as IPAH from 2006 to 2008 and 250 controls were included in the study. VIP gene variants were screened by direct sequencing, and VIP serum level was determined by enzyme-linked immunosorbent assay. Clinical and hemodynamic data of all patients were also obtained. The variant g.8129T→C in exon 7 was found to be the only variant in the coding region of VIP gene with a significantly higher frequency in patients (40.7%) than in control samples (15.2%). Moreover, there was marked difference in VIP serum level and hemodynamic data between IPAH patients with and without the variant. The variant g.8129T→C in exon 7 of VIP gene was correlated with the clinical phenotype of lower VIP serum level, higher mean pulmonary artery pressure and pulmonary vascular resistance in patients with IPAH comparing to those in patients without this variant. The VIP gene variant g.8129T→C may be one of the risk factors in the pathogenesis of IPAH.