The aim of this study was to determine whether orosomucoid1- like 3 (ORMDL3) single nucleotide polymorphisms rs7216389, rs11650680, rs12603332 are associated with susceptibility to asthma. We performed a meta-analysis by searching PubMed, EMBASE, Elsevier and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. We examined the association between the three SNPs and asthma risk in four genetic models (TT + TC vs. CC, TC vs. CC, TT vs. CC, TT vs. TC + CC). Thirteen published case-control studies involving 6462 cases and 7357 controls were included. Our meta-analysis indicated that rs7216389 was significantly associated with increased asthma risk in overall population. Subgroup analysis by age indicated significant association between the rs7216389 and asthma in children. Moreover, ORMDL3 rs11650680 was significantly associated with decreased asthma risk in dominant model (TT + TC vs. CC), and rs12603332 was significantly associated with decreased asthma risk in 3 models (TT + TC vs. CC, TC vs. CC and TT vs. CC). To Conclude, ORMDL3 rs7216389 polymorphism is associated with susceptibility to asthma. Children with variant T allele (TT or TC) and adults with TT homozygote in rs7216389 are at high risks to suffer from asthma. However, people with T allele in rs11650680 or rs12603332 are protected from asthma.