A simple and selective high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of two anti-hypertensive drugs like Hydrochlorothiazide (HCT) and Alfuzosin (ALF). Separation was achieved using C18 column (4.6, 250 mm) with isocratic elution of the mobile phase composed of methanol and water with the ratio of 90 : 10 at a flow rate of 1 mL/min. The optimized wavelength for the measurement of HCT and ALF is 260 no. Quantification was based on measuring the peak areas. Two compounds were resolved with retention times of 1.7 and 2.5 min for HCT and ALF, respectively. Analytical performance of the proposed HPLC procedure was statistically validated with respect to linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantification. The linearity ranges were 2-10 μg/mL for HCT and ALF with correlation coefficients >0.999. The developed method was found to be accurate, precise for simultaneous determination of HCT and ALF in tablets. © 2015 Scientific Publishers. All Rights Reserved.