AIM: To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with retinopathy of prematurity (ROP) risk among Chinese infants. METHODS: Nine polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and 878 prematurely-born infants of low birth weight who were without any ophthalmologic disease. The frequencies of the polymorphisms were compared between cases and controls to identify the association present, if any. RESULTS: Of the nine polymorphisms, only two showed significant associations: ACE insertion deletion (ID) polymorphism (P=0.031) and TNF -308G/A polymorphism (P<0.001). The former was associated with a reduced ROP risk [ID genotype, adjusted OR (aOR): 0.603, 95%CI: 0.427-0.893, P=0.034; DD genotype, aOR: 0.468, 95%CI: 0.229-0.626, P=0.002], while the latter showed an increased risk (GA genotype, aOR: 1.956, 95%CI: 1.396-2.465, P<0.001; AA genotype, aOR: 2.809, 95%CI: 1.802-4.484, P<0.001). The association was also noted at the allele level (ACE D allele aOR: 0.698, 95%CI: 0.294-0.883, P<0.001; TNF -308A allele aOR: 1.776, 95%CI: 1.446-2.561, P<0.001). CONCLUSION: The ACE ID polymorphism can protect against ROP development while the TNF -308G/A can increase the risk of the disease among Chinese infants.