A simple, rapid, precise, sensitive and reproducible reverse phase high performance liquid chromatography (RP-HPLC) method has been developed for the quantitative analysis of Ambrisentan and Tadalafil in pharmaceutical dosage form. Chromatographic separation of Ambrisentan and Tadalafil was achieved on Shimadzu HPLC accomplished with cyber lab LC 100 software by using Cap cell pack C18 column and the mobile phase containing 1ml Triethyl amine is dissolved in 1lt water adjust pH-7.0 with OPA & ACN in the ratio of 60:40% v/v. The flow rate was 1.0 ml/min; detection was carried out by absorption at 249nm using a photodiode array detector at ambient temperature. The number of theoretical plates and tailing factor for Ambrisentan and Tadalafil were NLT 2000 and should not more than 2 respectively. % Relative standard deviation of peak areas of all measurements always less than 2.0. The proposed method was validated according to ICH guidelines. The method was found to be simple, economical, suitable, precise, accurate & robust method for quantitative analysis of Ambrisentan and Tadalafil. Key words: HPLC, Ambrisentan and Tadalafil.