A simple, specific, accurate and precise stability indicating reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous estimation of Aspirin and Isosorbide 5-mononitrate in bulk drug and its pharmaceutical dosage form. A chromatographic separation was achieved with reverse phase phenomenex® Luna 5µ C18 (2) 100A (250 × 4.60 mm) column in an isocratic mode at ambient temperature. The mobile phase consisting of water: methanol: acetonitrile (55:28:17% v/v/v) at a flow rate of 1 ml/min. The eluents were monitored at 217 nm. The retention times of Aspirin and Isosorbide 5-mononitrate were found to be 2.05±0.056 min and 4.27±0.016 min respectively. The regression analysis revealed linearity in the concentration range of 1-10 µg/ml and 1-10 µg/ml for Aspirin and Isosorbide 5-mononitrate respectively. The method was validated in terms of linearity, accuracy, precision, limit of detection (LOD), limit of quantification (LOQ) in accordance with ICH guide lines. The results of the study showed that the developed method is simple, precise and accurate, and therefore suitable for routine analysis of these drugs in pharmaceutical dosage form.