A stability- indicating ultra Performance liquid chromatography (UPLC) method has been developed and validated for the simultaneous determination of Aspirin and Esomeprozole Magnesium in pharmaceutical preparations. An Agilent Zorbax XDB column (50X4.6mm i.d., 1.8μm particle size) was used. The mobile phase consisted of a mixture of 0.2% ortho Phosphoric Acid, methanol and acetonitrile in simple gradient elution Ultraviolet (UV) detection was performed at 210 nm. Total run time was 6 min; these two drugs were eluted at the retention times of 2.4 and 2.8 min for Esomeprozole Magnesium and Aspirin respectively. The method was validated in terms of linearity, range, specificity, accuracy, and precision, limit of detection (LOD) and limit of quantitation (LOQ). The linearity for both the drugs was found in the range of 32.5-97.5 μg mL-1of Asp and 4-12 μg mL-1 for Eso. The % recoveries of Aspirin and Esomeprozole Magnesium were found to be 99.41 and 101.11, respectively. The utility of the procedure is verified by its application to marketed formulations that were subjected to accelerated degradation studies. The method distinctly separated the drug and degradation products even in actual samples. The products formed in marketed tablet dosage forms are similar to those formed during stress studies.