<i>Background:</i> Polyvinylchloride (PVC) is often adopted for making medical devices. <i>Objective:</i> Testing the hypothesis that materials degradation occurs in PVC endotracheal tubes during infant ventilation, thus releasing the known toxic plasticizer di-(2-ethylhexyl)phthalate (DEHP). <i>Materials and Methods:</i> Endotracheal tubes degradation was assessed by: (1) analysis of color and spectral changes in endotracheal tubes after use in the 400- to 700-nm range and compared to virgin samples. Color changes were expressed as euclidean distances in the Commission International de l’Eclairage Laboratory and Lightness-Chroma-Hue (Munsell’s) color spaces (i.e., ΔE, ΔL, Δa, Δb, ΔC, and ΔH units); (2) DEHP leakage was assessed by thermal characterization by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). Data from used tubes were compared with those from either virgin devices or submitted to artificial aging, including O₂-induced oxidation, washing, UV photodegradation and exposition to acid solutions. <i>Results:</i> Significant color differences of 13.33 ± 0.85 ΔE were evidenced in used endotracheal tubes, as compared to virgin samples (p < 0.0001). Chromatic changes were independent from intubation duration. DSC and TGA analyses showed a loss of DEHP from used tubes, as indicated by increase of the glass transition temperature (Tg) and DEHP weight loss. In vivo application of tubes was associated with an aging process whose effects on the optical and spectral properties were similar to those observed following artificial aging processes. <i>Conclusions:</i> Our findings indicate that significant spectrocolorimetric, DSC and TGA changes occur in endotracheal tubes after application, thus demonstrating for the first time the occurrence of in vivomaterials degradation and DEHP leakage from medical devices worldwide used for neonatal ventilation.