Over the years, numerous researchers have explored the relationship between ischemic stroke (IS) and interleukin-18 (IL-18) gene polymorphisms. However, those studies reported conflicting and ambiguous results. The effects of IL-18 (137G/C and 607C/A) genetic variants on IS were investigated in this article. We performed a systematic search that was comprehensively executed in online databases for studies published up to 30 April 2018. Calculation of pooled odds ratios (ORs) and 95% confidence intervals was applied to assess the intensity of correlation using Stata.12.0. The overall outcome showed that 137G allele increased the risk of IS under the homozygous model (OR=1.36, P=0.027). Nevertheless, on the basis of ethnicity for the subgroup analysis (Asian and Egyptian), it was disclosed that the association was only found in the Egyptian population under the allelic model (OR=2.72, P=0.001) and recessive model (OR=5.04, P=0.000). In the overall analysis, 607C allele increased the risk of IS under all hereditary models (C vs. A: OR=1.26, P=0.002; CC vs. AA: OR=1.67, P=0.002; CA vs. AA: OR=1.30, P=0.001; CC+CA vs. AA: OR=1.41, P=0.000; CC vs. AA+CA: OR=1.48, P=0.000); a similar trend was observed in the Asian population. However, 607C allele was linked to decreased IS risk in the Egyptian population under all genetic models except the heterozygous model (C vs. A: OR=0.48, P=0.006; CC vs. AA: OR=0.19, P=0.007; CA vs. AA: OR=0.47, P=0.078; CC+CA vs. AA: OR=0.39, P=0.020; CC vs. AA+CA:OR=0.30, P=0.030). Although two polymorphisms were associated with IS, the association varied significantly in different countries. Large epidemiological studies will be required to verify these findings in the future.