In this study, reverse phase high performance liquid chromatographic method have been developed and validated for the simultaneous determination of aspirin and omeprazole. The chromatographic separation was achieved in a Zorbax Eclipse XDB- C18 (4.6 × 250 mm × 5 μ) as a stationary phase Acetonitrile: Water (50:50, v/v) as mobile phase at a flow rate of 1 ml/min. UV detection was performed at 293 nm. The retention time of aspirin and omeprazole was found to be 3.260 and 1.787 min respectively. The results of analysis were validated statistically and by recovery studies. Linearity, accuracy and precision were acceptable in the ranges (2-14 μg/ml) for aspirin and (2-18 μg/ml) for omeprazole. The % recovery for aspirin and omeprazole was 99.79 and 99.61, respectively. The results of the studies showed that the proposed Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method was simple, rapid, precise and accurate, which can be used for the routine determination of aspirin and omeprazole.