S (-) Pantoprazole and Mosapride Citrate are used in combined dosage form for treating various gastrointestinal disorders, particularly for hyperacidity which is frequently associated with gastrointestinal dysmotility. Present research work was undertaken to develop and validate a novel, rapid, accurate, sensitive, precise and stabilityindicating reverse-phase High-performance liquid chromatographic method (RP-HPLC) for simultaneous determination of S(-)Pantoprazole and Mosapride Citrate in capsule formulation. The chromatographic separation was achieved with the use of ACE3, C8, 100x4.6mm, 3μ analytical column at 35°C employing a gradient elution. Mobile phase consisting of Solution–A (20mM Ammonium acetate buffer of pH 5.5+ 0.05) and Solution-B (Acetonitrile) used at a flow rate of 1.0mL/min with injection volume of 10μL and the detection was done at 278nm using UV detector. The retention times of S (-) Pantoprazole and Mosapride were found to be 3.5 min and 6.7 min respectively. The method was validated for System suitability criteria, specificity, accuracy, precision, linearity, filter validation and solution stability. The results obtained are well within limit as per ICH guideline. In addition, the proposed method was effectively applied for the routine analysis of QC samples.