Roflumilast (RFL), a newly approved and highly selective phosphodiesterase 4 inhibitor for the treatment of severe chronic obstructive pulmonary disease, associated with chronic bronchitis and a history of numerous exacerbations. The main objective of this work was to evaluate the simultaneous (TG/DSC) thermoanalytical characterization and compatibility of roflumilast with the widely used excipients for solid dosage form employing differential scanning calorimetry (DSC), thermogravimetric analysis (TG), optical microscopy, isothermal stress testing (IST) by HPLC and liquid chromatography–mass spectrometer techniques with Fourier transform infrared spectroscopy (FT-IR) as a complimentary technique to contribute in the interpretation of results. The selected excipients were pregelatinized starch (PS), magnesium stearate, croscarmellose sodium (CCS), microcrystalline cellulose (MCC) and sodium starch glycolate (SSG). The DSC curve showed a sharp endothermic melting peak at 160.43 °C for roflumilast. On the basis of the DSC results, some interactions were found with RFL–CCS, RFL–MCC, RFL–SSG and RFL–PS. However, during IST studies less than 2% change in roflumilast content was observed in all stressed physical mixtures except RFL–SSG (<14%) which showed incompatibility with roflumilast. These results would be suitable for formulation development of the film-coated tablets of roflumilast.