Peroxisome proliferrator-activated receptor gamma coactivator-1alpha (PGC-1alpha; PPARGC1A) is a coactivator of the nuclear hormone receptor family that participates in the transcriptional programme of lipid metabolism and oxidative stress implicated in atherogenesis. Therefore, in the present study, we investigated PPARGC1A polymorphisms in the prevalence of coronary artery disease (CAD). A case-control study comprising 342 patients with CAD and 334 controls was performed in a Chinese population. Two single nucleotide polymorphisms (Gly482Ser and Thr394Thr) in the PPARGC1A gene were genotyped and compared using the polymerase chain reaction-restriction fragment length polymorphism method. The XA (GA + AA) genotype of Gly482Ser displayed a higher frequency in CAD patients than that in control subjects (P = 0.019; adjusted odds ratio = 1.53; 95% confidence interval 1.06-2.20). No significant difference in Thr394Thr genotype distribution or in Gly482Ser-Thr394Thr haplotype combinations was found between CAD patients and controls. Furthermore, we found that the significantly increased risk of CAD associated with the XA genotypes of Gly482Ser was more evident among subjects who were younger than 64 years of age, female, overweight and with hypertension. The results indicate that the PPARGC1A Gly482Ser polymorphism may contribute to the risk of CAD in the Chinese population investigated.