The cytochrome P450 2D6 (CYP2D6) is the most highly polymorphic isoenzyme of the cytochrome P-450-system, which affects the metabolism of one-fourth of all prescription drugs. Tramadol, a narcotic-like pain reliever used to treat moderate to severe pain, is primarily metabolized by CYP2D6. The CYP2D6*10 allele is the most common allele in the Chinese population. Therefore, we investigated the effects of CYP2D6*10 on tramadol pharmacokinetics in 45 post-operative patients who had undergone gastrointestinal tract surgery. Tramadol was administered to the patients after the operation, and the plasma concentrations of tramadol and O-desmethyltramadol were subsequently evaluated at 12 time points. Pharmacokinetic analyses were performed using non-compartmental methods. The area under the curve (AUC), plasma clearance (CL), elimination half-life (T1/2), mean residence time (MRT), peak concentration, and peak time of tramadol and O-desmethyltramadol were calculated. CYP2D6*10 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequency of CYP2D6*10 alleles was 51% in the 45 patients. The patients were divided into three groups according to their CYP2D6*10 genotype: wild-type, heterozygous, and homozygous mutant. Pharmacokinetic parameters were compared among the three groups. The analyses showed that T1/2, MRT, and AUC of tramadol were larger, and CL was lower in homozygous mutant patients compared to the wild-type group (P< 0.05). These results show that the CYP2D6*10 genetic polymorphism has a significant impact on the pharmacokinetics of tramadol in Chinese post-operative patients.