A fast, high-performance liquid chromatography method was established to estimate Oxymetazoline hydrochloride and Isoxsuprine hydrochloride in pharmaceutical preparations HPLC. It consists of an Azorbax-C8 (250mm ×4.6 mm, 5µm ) column with a mobile phase composed of methanol:acetonitrile: buffer (0.01 M) potassium dihydrogen phosphate with triethylamine (pH 5.5) (50: 10:40, V/V/V ) eluted at 1.5 ml/min flow rate. The detection was done using a photodiode array (PDA) detector. The proposed method was validated in linearity, precision, and accuracy. The retention times of IsoxsuprineHCl and OxymetazolineHCl are 3.6 and 6.2 ±0.4 min, respectively. For both drugs, the linear range and detection limits were 1-250 µg/ml and 0.5 µg/ml, respectively. The proposed method was successfully applied to determine ISX and OXY in pharmaceutical preparations.