A simple, Accurate, precise method was developed for the simultaneous estimation of the Prazosin and Polythiazide in Tablet dosage form. Chromatogram was run through Std Discovery C18 150 x 4.6 mm, 5µ. Mobile phase containing Buffer 0.1%OPA: Acetonitrile taken in the ratio 60:40 was pumped through column at a flow rate of 1 ml/min. Buffer used in this method was 0.1% OPA buffer. Temperature was maintained at 30°C. Optimized wavelength selected was 270.0 nm. Retention time of Prazosin and Polythiazide were found to be 2.316 min and 3.176. %RSD of the Prazosin and Polythiazide were found to be 0.5 and 0.7 respectively. %Recovery was obtained as 100.49% and 100.40% for Prazosin and Polythiazide respectively. LOD, LOQ values obtained from regression equations of Prazosin and Polythiazide were 0.079, 0.240 and 0.03, 0.08 respectively. Regression equation of Prazosin is y = 50050.x + 7773 and of Polythiazide was y = 95434.x + 6175. Retention times were decreased and run time was decreased, so the method developed was simple and times were decreased and run time was decreased, so the method developed was simple and economical that can be adopted in regular Quality control test in Industries.