Objective To investigate the prevalence and implication of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) variants and vitamin K epoxide reductase complex, subunit 1 (VKORC1)-1639G>A polymorphisms in Chinese patients receiving warfarin therapy. Methods Chinese Han patients requiring oral warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2, *3, *4, *5 variants and VKORC1-1639G>A polymorphisms, fourth-day international normalized ratios (INRs) and warfarin maintenance dose were investigated. Results Out of 101 patients, there were no significant differences in fourth-day INR or warfarin daily maintenance doses between patients with CYP2C9*1*1 and CYP2C9*1*3 genotypes. Patients with the VKORC1-1639 AA genotype had a higher fourth-day INR (1.870.14) than those with the VKORC1-1639 AG genotype (1.32 +/- 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA genotype (2.40 +/- 0.70mg/day) was significantly lower than for patients with the VKORC1-1639 AG genotype (4.83 +/- 0.70mg/day). Conclusions Unlike Caucasian populations, VKORC1-1639G>A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.