Saminathan kayarohanam, Bino Kingsley, Sivaramakrishnan and G. Nagarajan Esomeprazole is chemically bis (5methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl]sulfinyl]- 1Hbenzimidazole-1-yl). It is a gastric proton-pump inhibitor (PPI) used in treatment of gastric-acid related diseases. A Simple, sensitive, selective and accurate reverse phase high performance liquid chromatographic (RP-HPLC) methods were developed, estimated and validated for the analysis of Esomeprazole sodium in bulk and injection forms. The chromatographic separation was performed by the using C8, column having 250 x 4.6mm 5μm. Using mobile phase containing Acetonitrile and phosphate buffer (58:42v/v) adjusted to PH 7.6 with phosphoric acid. The analysis was run at a flow rate of 1.5ml/min and injection volume was 20 µL. The detection was monitored at 280nm. The retention time of Esomeprazole was 2.93 min. The developed method was validated for precision, intermediate precision (ruggedness), linearity, specificity, accuracy, and stability. Recovery of Esomeprazole in formulations was found to be in the range of 99.08%, 100.86%, and 101.52% respectively. And the correlation coefficient was 0.999. Hence, it was concluded that the developed method is suitable for routine analysis due to its less analysis time. International Journal Of Pharmacy 2249-1848 2014-04-04 2 183-188 Copyright (c) Pharma Scholars. All rights reserved 2013