A new simple, rapid, isocratic and stability indicating reverse phase high performance liquid chromatography (HPLC) method has been developed for simultaneous estimation of pioglitazone (P), amlodipine (AM), atorvastatin (AT) and clopidogrel (CP). Isocratic separation was achieved on Millennium M Sil C18 (125 mm ´4.6 mm) column, with mobile phase comprising of methanol: 0.02 M KH2PO4 (55:45 V/V), pH adjusted 4.0 with 0.01% ortho phosphoric acid. The flow rate was maintained 1mL/min and analytes were screened with U.V. detector. The method was validated according to ICH guidelines with respect to linearity, accuracy, precision and specificity. The drugs were exposed to various stress conditions like acidic and basic hydrolysis, oxidation, exposure to UV light and temperature (dry heat) and the stressed sample were analysed by the proposed method. No co-eluting, interfering peaks from excipients, impurities were observed during stress condition and all the degraded peaks are well resolved from parent peaks.