A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32-3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.