<i>Background:</i> Recently, the C1019T polymorphism in the human gene encoding connexin 37 (CX37, encoded by <i>GJA4</i>) has been reported to be associated with coronary artery disease (CAD)/myocardial infarction in different racial groups, but no data are currently available in northern Han Chinese. The aim of our study is to investigate the association between 3 <i>GJA4</i> gene polymorphisms (–1930C/T, C1019T and I1297D) and the susceptibility to CAD in northern Han Chinese. <i>Methods:</i> 502 CAD patients and 410 controls confirmed by coronary angiography were genotyped by polymerase chain reaction restriction fragment length polymorphism analysis in an independent case-control study. <i>Results:</i> The overall distribution of <i>GJA4</i> C1019T genotypes among CAD patients and healthy controls was significantly different (p < 0.01). Frequencies of C1019T CC homozygote and C allele were significantly higher in the patient group than those in the control group. Stratification analysis showed that the C1019T C allele significantly increased the risk of CAD only among male subjects (p = 0.006; OR 1.38; 95% CI 1.09–1.74). After adjustment for conventional risk factors, binary logistic regression analysis showed that the C allele carrier (CC + CT) of C1019T was an independent risk factor for CAD (p < 0.05). Further linkage disequilibrium tests and haplotype analysis revealed that the C-C-D haplotype conferred an increased risk of CAD. <i>Conclusions:</i> Our study suggests that <i>GJA4 </i>gene C1019T polymorphism and/or its related C-C-D haplotype might contribute to an increased risk of CAD and potentially play an important role in the development of coronary atherosclerosis in northern Han Chinese.