There are two genotypes of the vacA intermediate region, il and i2; however, the association between the genotypes and gastroduodenal disease remains to be elucidated. The aim of this article was to investigate the interaction between the genotypes and H. py/ori-associated diseases such as chronic gastritis, peptic ulcer disease (PUD) and gastric cancer. Methods: The meta-analysis was performed in Review Manager 4.2.2. Results: Eleven (ten articles and one abstract) met the inclusion criteria and were included. The il genotype increased the risk of PUD (OR = 1.70, 95% CI: 1.24-2.33, P 〈 0.001) and gastric cancer (OR = 3.90, 95% CI: 2.64-5.78, P 〈 0.001). Sub-analysis showed that the il genotype was significantly associated with gastric ulcers (OR = 2.59, 95% CI: 1.05-6.35, P = 0.040), but not with duodenal ulcers (OR = 1.04, 95% CI: 0.61-1.76, P = 0.90). In addition, the association between the il genotype and PUD and GC existed in studies not only from Europe but also Asia, except for the association between the il genotype and PUD in Asian population. Conclusion: The vacA il genotype is associated with an increased risk of the development of peptic ulcer disease (mainly gastric ulcer) and gastric cancer. In geographical distribution, the association between the il genotype and PUD and GC existed in studies not only from Europe but also Asia, except for the association between the il genotype and PUD in Asian population.