A rapid, precise, accurate, specific and simple RP-HPLC method was developed for the simultaneous estimation of Tezacaftor and Ivacaftor in bulk and its combined pharmaceutical dosage form. A High-performance liquid chromatography Waters, software: Empower 2, 2695 separation module, 996 PDA detector, using Symmetry C18 (4.6×150mm, 5µ) column, with mobile phase composition of methanol: TEA buffer in proportion 40:60 v/v was used. The flow rate of 1.0 mL min-1 and effluent was detected at 260 nm. The retention time of Ivacaftor and Tezacaftor was found to be 2.781 minutes and 4.048 minutes respectively. Linearity was observed over concentration range of 5-25µg ml-1 for Ivacaftor and 25-125µg ml-1 for Tezacaftor respectively. The accuracy of the proposed method was determined by recovery studies and the Ivacaftor was found to be 99.8% and Tezacaftor was found to be 99.4% respectively. The proposed method is applicable to routine analysis of Ivacaftor and Tezacaftor in bulk and pharmaceutical formulations. The proposed method was validated for various ICH parameters like linearity, limit of detection, limits of quantification, accuracy, precision, range and specificity. Key Words: Ivacaftor, Tezacaftor, RP-HPLC, Robustness and ICH Guidelines.