Objective(s): Previous studies have reached different conclusions regarding an association between apolipoprotein E (APOE) polymorphisms and depression. This meta-analysis was designed to clarify these controversies. Materials and Methods: Literatures were identified reviewing the national and international databases. The eligible articles for meta-analysis were determined by quality assessment and implementation of inclusion/exclusion criteria. This meta-analysis was performed using Review Manager 5.2 software. The odds ratios (ORs) with corresponding 95% confidence interval (CIs) were calculated using a fixed effects model. Funnel plots and Egger's regression tests were used to assess the publication bias. Results: A total of nine studies that met the inclusion criteria were identified by performing a comprehensive search on the association between APOE polymorphisms and depression. APOE epsilon 4 allele was significantly associated with depression (allele: OR=1.36, 95% CI=1.11-1.66, P=0.003; dominant: OR=1.34, 95% CI=1.06-1.68, P=0.001; recessive: OR=1.11, 95% CI=0.45-2.76, P=0.82). HAMD scores were higher in depression patients with-APOE epsilon 4 genotype than who without-APOE epsilon 4 genotype (OR=0.96, 95% CI=0.16-1.76, P=0.02). Conclusion: APOE epsilon 4 allele increased the depression risk; depressive patients carrying APOE epsilon 4 allele had more severe depressive symptoms.