Combination therapy of calcipotriol monohydrate (CPM) and betamethasone dipropionate (BMD) is the option of choice for treatment of psoriasis. Psoriatic patients suffer from chronic dermatitis characterized by scaling, infiltration and erythema. The presant work is aimed at developing a validated RP-HPLC method for the simultaneous estimation of calcipotriol monohydrate (CPM) and betamethasone dipropionate (BMD) by using most affordable materials and techniques. Initially the mobile phase tried was methanol: Ortho phosphoric acid buffer and Methanol: phosphate buffer, Acetonitrile: methanol with various combinations of pH as well as varying proportions. Finally, the mobile phase was optimized to Phosphate buffer (pH 3.0), Ethanol in proportion 45 : 55 v/v respectively. The method was performed with various columns like C18 column Phenomenex column, YMC, and Inertsil ODS column. Dikma Endeversil C18 ODS (2.1x 150mm, 3 mm) was found to be ideal as it gave good peak shape and resolution at 0.3 ml/min flow and the retention times were found to be 3.724, 5.148min.. UV spectrum of 10 µg/ml Betamethasone and 10 µg/ml Calcipotriene in diluents (mobile phase composition) was recorded by scanning in the range of 1000nm to 400nm. From the UV spectrum wavelength selected as 254 nm. At this wavelength both the drugs show good absorbance. The method developed was subjected to system suitability, assay (betamethasone dipropionate-99.97%, calcipotriol monohydrate100.64%). Precision, accuracy, robustness LOD, LOQ and degradation studies and found the results are within limits. Keywords: betamethasone dipropionate, calcipotriol monohydrate, Acetonitrile, psoriasis etc.