ABSTRACT A straightforward and accurate method was devised for simultaneously determining Drospirenone and Estetrol in tablet dosage form. The chromatogram was generated using a Kromosil C18 column (150 x 4.6 mm, 5.0 mm), with a mobile phase consisting of Buffer 0.01N KH2PO4: Methanol in an 80:20 ratio, flowing through the column at a rate of 1.0 ml/min. This method utilized OPA as the buffer, and the temperature was maintained at 30°C. The optimized wavelength for detection was set at 263.0 nm. The retention times for Drospirenone and Estetrol were determined to be 2.597 min and 2.1336 min, respectively, with %RSD values of 0.4 for both compounds. The %Recovery was calculated as 100.25% for Drospirenone and 100.09% for Estetrol. The LOD and LOQ values were obtained from the regression equations of Drospirenone and Estetrol, resulting in 0.01 and 0.02 for LOD, and 0.08 and 0.25 for LOQ, respectively. The regression equations for Drospirenone were found to be y = 361228x + 6065.6, and for Estetrol, y = 341114x + 46689. The method exhibited reduced retention times and overall run time, indicating its simplicity and cost-effectiveness. This makes it suitable for routine quality control testing in various industries. Keywords: Drospirenone, Estetrol, RP-HPLC, Validation.