A Simple, sensitive, rapid, precise and accurate RP-HPLC method has been developed and validated for simultaneous estimation Aspirin and Lansoprazole in synthetic mixture. The Chromatographic separation was achieved on a Reversed-phase Phenomenax-luna C18 (250 x 4.6mm, 5 μm) column using a mobile phase consisting of Acetonitrile : Tris buffer : Methanol (30:40:30 % v/v/v) (pH 4.0) at a flow rate of 1.2 mL/min and UV detection at 280 nm. Developed method was validated according to ICH Q2 (R1) guidelines. The method was found to be linear between the range of 13.2 – 66.0 µg/ml for Aspirin and 2 - 10 µg/ml for Lansoprazole. The precision (intra-day, inter-day) data of this method was found to be within limits (% RSD < 2%). Accuracy was determined by recovery studies and % recovery found between 98 to 102%