The current study aimed to develop and new, simple, accurate, economical and stability-indicating RP-HPLC for simultaneous estimation of Amlodipine Besylate, Valsartan and its related substances in their film-coated tablets dosage form. Chromatographic system was performed on the YMC ODS-A C18 (150 mm × 4.6 mm, 5μm particle size) using a binary gradient elution consist of two solvent systems, solution (A) 0.02 monobasic sodium phosphate Adjust with phosphoric acid to a pH of 2.5. and solution (B) consisting of Solution A: Acetonitrile (45:55). at a flow rate of 1.0 mL/min, injection volume 10 µL, UV detection at 235 nm, column oven temperature 30 ºC and autosampler temperature 10 ºC. This method was validated according to ICH requirements for new methods, which include accuracy, precision, selectivity, robustness, ruggedness, LOD, LOQ, linearity and range. Linear relationships were obtained in the ranges of 10-300 µg/mL and 5-200 µg/mL with correlation coefficients of 0.9997 and 0.9998 for Amlodipine Besylate and Valsartan respectively. The forced degradation studies as acidity, alkalinity, oxidation, heat, thermal, humidity and photodegradation were performed according to ICH guidelines.