Objective This study aimed to evaluate the association between the paraoxonase (PON) genes variants and Alzheimer's disease (AD) using systematic review with meta-analysis.Methods Relevant studies were identified by searching English and Chinese databases extensively.Newcastle-Ottawa Scale (NOS) was employed to evaluate the quality of included studies.The odds ratio (OR) was calculated using a random-effects or fixed-effects model.A Q statistic was used to evaluate homogeneity,and fail-safe number,Egger's test and funnel plot were used to assess publication bias.Results A total of 15 studies were included and identified for the current meta-analysis.The NOS scores ranged from 7 to 8,meaning good quality of studies.It was found that the SS genotype of PON2 S311C polymorphism had an significant association with AD in the studied population (OR=0.82,P=0.04).However,there was no significant relationship between other three genetic variants of PON genes and AD.Conclusions Existing evidence indicated that the PON2 S311C polymorphism (SS genotype) was associated with risk of AD in studied population.Future studies with larger sample sizes will be necessary to confirm the present results.