To study the association of apolipoprotein E (APOE) polymorphisms and primary open-angle glaucoma (POAG).After a systematic literature search, all relevant studies evaluating the association between APOE polymorphisms and POAG were included. All statistical tests were calculated with Stata 11.0.Twelve independent studies on the APOE gene (1,971 cases, 1,756 controls) and POAG were included. A significant association between the APOE gene and POAG was found in the genetic model of ε4/ε4 versus ε3/ε3 (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.12-3.88, p = 0.02). However, no association was detected in the models of ε2/ε2 versus ε3/ε3, ε2/ε3 versus ε3/ε3, ε2/ε4 versus ε3/ε3, ε3/ε4 versus ε3/ε3, allele ε2 versus allele ε3, and allele ε4 versus allele ε3. Subgroup analyses showed that a statistically significant association between the APOE gene and the risk of POAG existed in the genetic model of ε4/ε4 versus ε3/ε3 in Asians (OR = 3.55, 95% CI = 1.06-11.87, p = 0.04). No association was identified between the APOE gene and the risk of POAG in Caucasians.The present meta-analysis indicated that the ε4/ε4 genotype is associated with increased risk of POAG in Asians.