Pathological changes in patient with thalassemia which are consequences of chronic anemia, requires increased cardiac output and eventually may produce hypoxia, hypertension and congestive heart failure. Propranolol is a non selective beta-adrenergic receptor blocking drug widely use for the treatment of cardiovascular diseases. The contribution of presystemic hepatic metabolism to the highly variable oral bioavailability of propranolol leads to different therapeutic effect.The drug was metabolized by oxidation,N-dealkylation and glucuronidation pathway. The oxidation product ; active metabolite (4-OH propranolol) was conjugated with glucuronide activated by UGT 1A6 to produce 4-OH propranolol-glucuronide. To examine the effects of UGT1A6 polymorphisms(UGT1A6*2) on the pharmacokinetics of propranolol in healthy volunteers and thalassemic patients, thirteen healthy volunteers and ten thalassemic patients with different UGT1A6 genotype including wild type; UGT1A6*1/*1, heterozygote; UGT1A6*1/*2 ; and homozygote; UGT1A6*2/*2 were enrolled the study. UGT1A6 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. After an overnight fast, the subjects received a single oral dose of 40 mg propranolol. Blood samples were collected before and at different time points after dosing. Urine output was collected for 24 hour. Propranolol (P) and propranolol–glucuronide (PG) concentrations in plasma and urine were determined using a validated high-performance liquid chromatography and gas chromatography-mass spectrometry method (GC/MS). 4-OH-propranolol glucuronide (HOP-G) in urine samples were also determined by GC/MS. Compared to wild type group, the healthy volunteers and thalassemic patients with heterozygote and homozygote showed the statistically significant increase of area under concentration-time curve (AUC0–∞), and maximum concentration (Cmax) of propranolol and decrease of Vd/F,and Cl/F. Lower PG/P and HOP-G/P plasma and urine ratio were noted. There was higher plasma concentration and longer half-life of propranolol in patients with wild-type than in volunteers with wild-type. These results demonstrated that the UGT1A6*2 appeared to exert statistically significant effects on the singledose pharmacokinetics of propranolol in both volunteers and thalassemic patients. The UGT1A6*2 decreased the enzyme activity resulting in higher plasma concentration and longer half-life of propranolol. The result from this study may useful for dose adjustment in the patient .