Purpose: In this study, the possible effects of CYP2C9 polymorphisms on the clinical response to losartan were investigated in a group of hypertensive patients. Materials and Methods: Seventy-four patients, newly diagnosed to have essential hypertension, and were subsequently prescribed losartan by attending physicians, were prospectively recruited for the study. Blood pressure measurements at the initiation of losartan treatment and six weeks after were completed for all participants. Genetic analysis for CYP2C9 polymorphisms was performed in blood samples collected at baseline. CYP2C9 *2 and *3 variant alleles were genotyped, and polymorphic patients' treatment responses were compared with the patients' who were carrying the wild type genotype. Results: Analysis comparing the wild type genotype and CYP2C9*1*2 genotype revealed a trend toward more systolic blood pressure reduction in favor of wild-type genotype. However, there was no statistically significant difference between these two groups considering the change in diastolic blood pressure levels. Regarding the CYP2C9*1*3 genotype, there were no significant differences in systolic or diastolic blood pressure changes. Conclusion: CYP2C9*1*2 polymorphism affects the systolic blood pressure response to losartan in hypertensive patients, while the CYP2C9*1*3 genotype was not shown in associated with systolic or diastolic blood pressure responses.