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Objective Many studies have showed that CCR5 was involved in the pathological process of acute graft-versus-host disease (aGVHD). However, the relationship between CCR5Δ32, a frameshift mutation, and grade 3-4 acute GVHD risk has not been well established. We performed a meta-analysis to explore the effects of CCR5 gene polymorphisms on grade 3-4 aGVHD. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched to collect relevant articles. Studies about association between CCR5 genotype in recipients or donors of allo-HSCT and aGVHD risk were included. All pooled analyses were based on fixed effects models. The effects were assessed from odd ratios (ORs) with 95% confidence intervals (CIs). Results A total of three studies comprising 937 recipients and 914 donors of allo-HSCT met the inclusion criteria. Compared with the wild-type CCR5 homozygotes, the pooled odd ratios (ORs) for CCR5Δ32 mutation (both homozygous and heterozygous) was 0.71 (95% CI, 0.40-1.26; P = .24) for donors, and 0.79 (95% CI, 0.35-1.81; P = .58) for recipients. No relationship was found between the presence of the CCR5Δ32 mutation and grade 3-4 aGVHD. Larger clinical investigations and retrospective studies are needed to explore the association of CCR5 gene polymorphisms with aGVHD risk as well as the outcome of HSCT. [ABSTRACT FROM AUTHOR]