Background Paraoxonase is known to play an important role in the pathophysiology of atherosclerosis. Genetic variants of the paraoxonase gene have been implicated as risk factors for atherosclerotic diseases such as coronary artery disease, but individual genetic association studies examining the relationship between the paraoxonase gene polymorphisms and ischaemic stroke have yielded inconsistent results. Aim This study aimed to evaluate the association between the paraoxonase gene variants and ischaemic stroke using systematic review with meta-analysis. Methods Relevant studies were identified by searching English and Chinese databases extensively. Allele and genotype frequencies for each included study were extracted. The odds ratio was calculated using a random-effects or fixed-effects model. A Q statistic was used to evaluate homogeneity, and Egger's test and funnel plot were used to assess publication bias. Results A total of 28 studies were included and identified for the current meta-analysis. It was found that the R allele or RR genotype of paraoxonase 1 Q192R polymorphism had an increased risk for ischaemic stroke in the general population (192R allele: odds ratio: 1.21, 95% confidence interval: 1.08-1.35, P = 0.0009 and 192RR genotype: odds ratio: 1.25, 95% confidence interval: 1.06-1.49, P = 0.009 in general population, respectively), but there was no significant association between other genetic variants of paraoxonase gene and ischaemic stroke. Conclusions Existing evidence indicates that the Q192R polymorphism (the R allele and RR genotype) is associated with an increased risk of ischaemic stroke in the general population. Future studies with larger sample sizes will be necessary to confirm the present results.