In the present study, we performed a meta-analysis of 10 eligible studies with 2683 HIV-1 patients and 3263 controls to elucidate the relationship between the VNTR polymorphism and HIV-1 infection risk. The strength of the present analysis is based on the accumulation of published data that provides enough information to generate a more precise conclusion. By using different genetic models, we could preliminarily estimate the effect of the allele frequency, genotype frequency, and homozygous proportion. The results indicated that the 5/5 homozygous genotype was associated with resistance to HIV-1 infection. The protective effect was most predominant in HIV-1 exposed seronegative (HESN) individuals. The stratified analyses by ethnicity and sample size confirmed these findings. Thus, it is important to emphasize that in studies concerning HIV-1 susceptibility, taking samples from HIV-1 exposed seronegative (HESN) individuals as controls may be more powerful than taking random healthy individuals as controls. In future studies, collecting both HIV-1 exposed seronegative individuals (HESN) and random healthy individuals as controls would be helpful for clarifying the relationship between candidate genes and host susceptibility to HIV-1 infection. But under the definition and criteria of HIV-1 exposed seronegative individuals (HESN), it is still a heterogeneous group. A workshop sponsored by NIH was conducted in 2011 and a consistent definition and criteria were drawn in the term of HIV-exposed seronegative (HESN) individuals [4] . In the following studies, the collection of the HESN as controls should strictly obey these definitions, which would be helpful in explaining natural HIV-1 protection in individuals exposed to HIV-1 who remain seronegative or demonstrate resistance to infection.