RP-HPLC method was developed for simultaneous estimation of Aspirin and Omeprazole using Phenomenex Luna C8 column (150×4.6mm, 5um) as stationary phase and Acetonitrile: Methanol: Buffer (25:10:65 pH2.5) as mobile phase at a flow rate 1.0ml/min and UV detection at 228nm.Aspirin and Omeprazole eluted at 4.6 &3.2 min respectively and showed linear response in conc. range of 20-100ug/ml and 10-50ug/ml with correlation coefficient for both the drugs (r²=0.999) ASP &OMP respectively. The developed method was validated with regard to linearity, accuracy, precision, selectivity, specificity, robustness and system suitability. LOD for Aspirin and Omeprazole is 1.23 and 1.25 respectively & LOQ for Aspirin and omeprazole is 4.12 & 4.18 respectively. The developed method was validated as per ICH guidelines. The RSD for precision were found to be less than 2%. The percentage recoveries obtained for Aspirin and Omeprazole 98-102 % respectively.