Simple, sensitive and accurate stability indicating analytical method for dronedarone has been developed and validated using RP-HPLC technique. Developed method is used to evaluate the assay and related substances of dronedarone drug substance and tablets (Multaq ® ). The drug substance was subjected to the stress conditions such as hydrolysis (acid and base), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH) prescribed stress conditions to show the stability-indicating the nature of the method. Significant degradation was observed during acid and base hydrolysis, and peroxide degradation. The major degredants were identified by LC-MS, FTIR and 1 H NMR spectral analysis. The chromatographic conditions were optimized using an impurity-spiked solution and the samples generated from forced degradation studies. In the developed HPLC method, the resolution between dronedarone, process-related impurities, (namely Imp-1, Imp-2, Imp-3, Imp-4, Imp-5, Imp-6, Imp-7, Imp-8, Imp-9, Imp-10 and Imp-11) and degradation products were found to be greater than 1.5. The eleven potential process related impurities were separated on an Ascentis ® Express C18 column (4.6 × 10 cm i.d., particle size 2.7 µm) at a flow rate of 1.2 mL·min -1 . The LC method employed a linear gradient elution and the detection wavelength at 220 nm. The chromatographic behavior of all the impurities was examined under variable compositions of different solvents, temperatures and pH values.