The combination of diflucortolone valerate (DIF) and isoconazole nitrate (ISO) is commonly used in pharmaceutical preparations. Though there are already few methods in the literature for the simultaneous determination of these two compounds, none of them involves the stability indicating property that is emphasized by the ICH guidelines. In the present study. a stability-indicating HPLC assay method was developed and subsequently validated for the simultaneous determination of diflucortolone valerate (DIF) and isoconazole nitrate (ISO) in their combined pharmaceutical cream formulations. Separation of active substances and their degradation products was achieved on an ACE column (150 x 4.6 mm id, 5 mu m particle size) with an isocratic mobile phase of sodium dihydrogen phosphate buffer and methanol mixture in the ratio of 27 : 73, v/v with UV detection at 240 nm. The chromatographic separation was performed in very short run time with a flow rate of 1.5 mL/min. The developed method was validated as per United States Pharmacopeia (USP) and International Conference on Harmonization (ICH) guidelines. DIF and ISO active substances were exposed to stress conditions separately and also in their combined drug product form in order to examine the stability indicating a property of the proposed method. Stressed samples were analyzed by using HPLC equipped with a photodiode array (PDA) detector and the method was found to be stability-indicating. Therefore, we introduced a facile method for routine analysis of DIF and ISO in combined cream pharmaceutical dosage forms and their corresponding stability studies.