A simple and rapid reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the estimation of loxoprofen sodium dihydrate (LSD) in tablets. An isocratic HPLC analysis was performed on Phenomenex, Luna C18(2) (250 × 4.6 mm, 5μ) column. The compound was separated with the mixture of 0.4% orthophosphoric acid and acetonitrile in the ratio of 45:55 (v/v) as a mobile phase at a flow rate of 1.0 mL/min. UV detection was performed at 210 nm. Run time per sample was 8 min with the retention time of 4.9 min. The system suitability parameters, such as theoretical plate count, tailing and% RSD between six standard injections were within the limits. The method was validated according to ICH guidelines. The method was validated for specificity, precision, linearity, stability of sample solution, intermediate precision, robustness and accuracy. The stability of the sample solution was checked for 24 h at one hour intervals. The results show that the sample solution is stable for at least 24 h. Calibration plots were linear over the concentration range of 10–90 μg/mL as indicated by the correlation coefficient of 0.9992. The% RSD was 0.115 and 1.288 for system precision and method precision, respectively. The % RSD values for intermediate precision studies were less than 2%. The robustness of the method was evaluated by deliberately altering the chromatographic conditions and the results were adhered with the limits. The high recovery and low relative standard deviation confirm the suitability of the method for the estimation of loxoprofen sodium dihydrate in tablets.