Pranlukast hydrate is an anti-asthmatic drug and used in the treatment of acute asthma. Stability-indicating RP-HPLC method for pranlukast hydrate has been developed and validated. The reverse phase high performance liquid chromatographic method was developed using Shimadzu Column: Kromosil 100 C18 (150 mm × 4.6 mm × 5 μm) and mobile phase Acetonitrile: 0.1% Glacial acetic acid (85: 15% v/v). Eluent was monitored with UV-detector at 262 nm with a flow rate of 0.5 mL/min, temperature maintained at 30°C. Stress testing was carried out in acidic, alkaline, oxidative, photolytic and dry heat degradation conditions. The method was validated as per the International Conference for Harmonization guidelines and includes specificity, accuracy, precision, linearity and limit of quantitation and detection parameters. A relative standard deviation <2% indicates the developed method was precise. The accuracy of the method was represented by recovery studies ranging between 99.41 and 99.72%. In acid, alkaline, oxidative stress conditions, pranlukast hydrate degrades significantly and in photolytic, dry heat, hydrolytic conditions remain stable. This proposed method is suitable for the analysis of pranlukast hydrate in its laboratory mixture.