A simple High Performance Thin Layer Chromatography (HPTLC) method has been developed and validated for determination of Aspirin (ASP) and Omeprazole (OME) simultaneously in tablet dosage form (Yosprala). The samples were applied on an aluminum TLC plate pre-coated with silica gel. For separation, Toluene: Ethyl Acetate: Methanol: Glacial acetic acid (2.0:6.0:0.5:0.1, v/v/v/v) was used as a mobile phase. The drugs were separated satisfactorily with Rf values of 0.38 ± 0.02 and 0.69 ± 0.01 for OME and ASP, respectively. Detection was performed densitometrically in absorbance mode at 280 nm. The regression analysis for the calibration plots showed linear relationship with R2 of 0.999 and 0.998 for ASP and OME, respectively in the concentration range of 200-1400 ng/spot for ASP and 100-700 ng/spot for OME. The limit of detection and quantitation were 17.33 and 52.53 ng/spot, respectively for ASP and 7.48 and 22.66 ng/spot, respectively for OME. The proposed developed HPTLC method can be applied for identification and quantitative determination of OME.