A number of published case-control studies reported that the apolipoprotein E (ApoE) gene polymorphism was associated with the mild cognitive impairment (MCI). However, previous reports still remain conflicting. To estimate the association between ApoE polymorphism and MCI susceptibility, we searched the electronic databases including PubMed, Wanfang, CNKI (China National Knowledge Infrastructure), VIP, and EMBASE to retrieve all available studies. A total of 18 studies with 2,004 cases and 3,705 controls were included in this meta-analysis. The pooled analysis based on selected studies showed that statistically significant risk association was found between ApoE gene polymorphism and MCI in overall population (4 vs 3: odds ratio [OR] =2.38, 95% confidence interval [CI]: 2.11-2.68; 4/4 vs 3/3: OR =4.45, 95% CI: 3.06-6.48; 2/4 vs 3/3: OR =2.57, 95% CI: 1.77-3.73; 3/4 vs 3/3: OR =2.31, 95% CI: 1.99-2.69). However, no significant association was detected in two genetic models: 2 versus 3 (OR =0.90, 95% CI: 0.77-1.05) and 2/2 versus 3/3 (OR =0.91, 95% CI: 0.50-1.65). Furthermore, ApoE 2/3 genotype provided a slight protection for MCI in overall population (2/3 vs 3/3: OR =0.80, 95% CI: 0.66-0.97). In the stratified analysis based on ethnicity, similar results were also observed in Chinese population (significant risk: 4 vs 3: OR =2.52, 95% CI: 2.19-2.90; 4/4 vs 3/3: OR =5.45, 95% CI: 3.41-8.70; 2/4 vs 3/3: OR =2.59, 95% CI: 1.74-3.86; 3/4 vs 3/3: OR =2.34, 95% CI: 1.97-2.79; slight protection: 2/3 vs 3/3: OR =0.79, 95% CI: 0.64-0.98; no association: 2 vs 3: OR =0.92, 95% CI: 0.78-1.09; and 2/2 vs 3/3: OR =1.04, 95% CI: 0.55-1.99). In summary, this meta-analysis of 5,709 subjects suggested that ApoE 4 allele was associated with an increased risk of MCI. In addition, ApoE 2/3 genotype provided a slight protection for MCI.