Most of the drugs in multi component dosage forms can be analyzed by HPLC method because of the several advantages like rapidity, specificity, accuracy, precision and ease of automation in this method. An accurate, simple, reproducible and sensitive method for the simultaneous estimation of Esomeprazole and Itopride in the capsule was developed. This method employed Buffer (Ammonium Acetate, pH-5.5): Water: Methanol (25:15:60) as mobile phase. Phenomenex C18 column was used and the Spectrophotometric determination was done at 275 nm. The method was validated for linearity, precision, solution stability, repeatability, reproducibility, accuracy, robustness, system suitability, limit of detection and limit of quantification.