The Golgi SNAP Receptor Complex Member 2 (GOSR2) gene is a Golgi-associated soluble factor attachment receptor (SNARE) protein. Some single-nucleotide polymorphisms (SNPs) in the GOSR2 gene have been found to be associated with myocardial infarction (MI). The aim of the present study was to assess the association between the human GOSR2 gene and MI using a haplotype-based case–control study. A total of 238 MI patients and 284 controls were genotyped for the five SNPs used as genetic markers for the human GOSR2 gene (rs197932, rs3785889, rs197922, rs17608766, and rs16941382). Data were analyzed for three separate groups: the total subjects, men, and women. The overall distribution of the haplotypes in the total subjects and the men was significantly different between the MI patients and the control subjects (p=0.001, p=0.005, respectively). Additionally, the frequency of the T-G-G haplotype (rs197932-rs3785889-rs197922) for men was significantly lower in the MI patients than in the control subjects (p=0.040). Multiple logistic regression analysis also revealed that the frequency of the subjects with the T-G-G haplotype (homozygous and heterozygous diplotypes) was significantly lower compared with subjects without this haplotype in men after adjustment for the major confounding factors (odds ratio=0.455, p=0.041). The results of this study indicate that the T-G-G haplotype may be a protective genetic marker for MI in Japanese men.