Purpose Affinisol HPMC HME is a new popular form of hypromellose specifically designed for the hot melt extrusion and 3D printing of pharmaceutical products. However, reports of its thermal stability include only data obtained under inert N-2 atmosphere, which is not consistent with the common pharmaceutical practice. Therefore, detailed investigation of its real-life thermal stability in air is paramount for identification of potential risks and limitations during its high-temperature processing. Methods In this work, the Affinisol HPMC HME 15LV powder as well as extruded filaments will be investigated by means of thermogravimetry, differential scanning calorimetry and infrared spectroscopy with respect to its thermal stability. Results The decomposition in N-2 was proceeded in accordance with the literature data and manufacturer's specifications: onset at similar to 260 degrees C at 0.5 degrees C.min(-1), single-step mass loss of 90-95%. However, in laboratory or industrial practice, high-temperature processing is performed in the air, where oxidation-induced degradation drastically changes. The thermogravimetric mass loss in air proceeded in three stages: similar to 5% mass loss with onset at 150 degrees C, similar to 70% mass loss at 200 degrees C, and similar to 15% mass loss at 380 degrees C. Diffusion of O-2 into the Affinisol material was identified as the rate-determining step. Conclusion For extrusion temperatures >= 170 degrees C, Affinisol exhibits a significant degree of degradation within the 5 min extruder retention time. Hot melt extrusion of pure Affinisol can be comfortably performed below this temperature. Utilization of plasticizers may be necessary for safe 3D printing.