The ubiquitin-conjugating enzyme 2B gene (UBE2B) is involved in the regular and symmetric organization of the fibrous sheath of sperm flagella. This study aimed to examine the relationship between single nucleotide polymorphisms (SNPs) in UBE2B and infertility in Northeast Chinese men. We carried out a polymerase chain reaction-restriction fragment length polymorphism analysis for SNPs in 312 fertile males and 388 infertile males in Northeast China. Taking advantage of the high degree of linkage disequilibrium among SNPs surrounding UBE2B (r(2) > 0.90), we selected 2 haplotype-tagging SNPs with a minor allele frequency of 5% or greater (rs17167484: g.-293T>G and rs3777373: g.20016A>G) that captured the majority of the genetic variations in a 40-kbp region of this gene. No significant differences between cases and controls were found in the allelic and genotype distribution of the 2 SNPs. However, the haplotype analysis for the 2 SNPs showed that the GA haplotype was significantly associated with a greater than 3-fold decreased risk of male infertility (P = 0.003). Because the frequency of the GA haplotype (1.1%) is relatively low in Chinese men, such a significant finding may occur by chance, but the results are still significant after multiple comparison adjustments (P = 0.012 after Bonferroni's correction). We conclude that the UBE2B polymorphisms g.-293T>G, g.20016A>G and g.9157A>G are not associated with male infertility, and the GA haplotype is likely a protective factor for male fertility in Northeast Chinese men.