A reverse phase HPLC method is developed for the determination of Esomeprazole and Domperidone in pharmaceutical dosage forms. Chromatography was carried out on a C18 column [4.6 x 100mm, 5mm, Make: BDS] using a mixture of potassium di hydrogen ortho phosphate buffer and acetonitrile (65:35 v/v) as the mobile phase at a flow rate of 1.3 ml/min. Detection was carried out at 298 nm .The retention time of Domperidone and Esomeprazole was 2.788 min and 3.485 min. The linearity was observed In range of 50-130 µg/ml and 60-140 µg/ml with a correlation coefficient of Domperidone and Esomeprazole were 0.999 and 0.999.the proposed method was validated for its linearity, accuracy, precision and robustness .The proposed method is simple, accurate, precise, and reproducible hence it can be applied for routine quality control analysis of Esomeprazole and Domperidone in pharmaceutical dosage form.