A simple High Performance Liquid Chromatographic (HPLC) method for separation and quantitative analysis of Sulfadoxine (SDX), Pyrimethamine (PYR) and Artesunate (ART) in bulk and in tablets by RP – HPLC with PDA detector has been established and validated. The HPLC separation was carried out by reverse phase chromatography on ODS Hypersil (250 mm × 4.6 μm, 5μm) column, with mobile phase composed of 0.1M Potassium dihydrogen phosphate buffer ( pH 2.2 – adjusted with orthophosphoric Acid) : Acetonitrile (55:45 v/v) in isocratic mode at a flow rate of 1.5 ml/min. The detection was monitored at 254 nm. The calibration curve for Artesunate, Pyrimethamine & Sulfadoxine was linear from 50 to 500 μg/ml, 10 to 60 μg/ml & 250 to 1500 μg/ml respectively. The intermediate precision was found within limits. The proposed method has adequate sensitivity, reproducibility and specificity for the determination of Artesunate, Sulfadoxine, & Pyrimethamine in bulk and its tablet dosage forms. LOD and LOQ for Artesunate were found to be 0.970μg/ml and 3.239μg/ml, for Sulfadoxine 0.221 and 0.735 and for Pyrimethamine were found to be 0.212 and 0.708. Accuracy and reproducibility were found to satisfactory. The suitability of this method for quantitative determination of these compounds was proved by validation in accordance with the requirements ICH guidelines. The method was used for routine analysis of these drugs in bulk and in formulation.