This study investigates the effects of different processing methods on the chemical composition of thermoplastic polyurethanes, focusing on isocyanates and extractable oligomers. Using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and gas chromatography/mass spectrometry (GC/MS), seven commercially available thermoplastic polyurethane samples are analyzed as unprocessed granulate, injection-molded, and 3D-printed parts. Diffuse reflectance infrared Fourier transform spectroscopy analysis enables direct identification and quantification of isocyanates. In two polyester-based materials, substantial isocyanate contents were detected after processing. In both cases, the concentrations exceeded the w = 0.1 % threshold defined by REACH Regulation (EU) 2020/1149 for monomeric diisocyanates, thereby underscoring the regulatory significance of processing-induced changes. Gas chromatography/mass spectrometry analysis complements these results by indirectly but quantitatively detecting the formation of oligomers during processing via methylene diphenyl diisocyanate. The highest isocyanate content determined was w = 1.16 % in an injection-molded sample. The comparison of both methods shows their complementary significance in isocyanate detection. The study highlights the importance of choosing the correct processing parameters and analytical techniques to ensure thermoplastic polyurethane integrity and reduce undesirable changes in material composition.