<p>Domestic pigs (<i>Sus scrofa domesticus</i>) have been an important animal model for preclinical studies of gene-based therapies related to the treatment of human genetic sensorineural hearing loss, due to their genetic and morphophysiological proximity to humans. However, such studies require general anesthesia, which may affect cochlear mechanics, distorting scientific data. Therefore, it is critical to examine cochlear amplifier responses over time in healthy pigs under anesthetic conditions. Twelve pigs were randomly assigned to receive commonly used anesthetics: propofol or isoflurane. Distortion product (DP) amplitudes (2ƒ₁ – ƒ₂) and tympanometry were assessed at four 15-minute intervals (<i>t</i>₁ to <i>t</i>₄), beginning 40&#xa0;min after anesthesia induction. While both groups exhibited a significant decline in DP amplitudes over time (<i>p</i> &lt; 0.001), propofol demonstrated greater stability after an initial decrease, whereas isoflurane resulted in a progressive decline (<i>p</i> = 0.010) and consistently higher inter-individual variability. Tympanometric analysis revealed increased peak admittance and pressure by <i>t</i>₄ in both groups (<i>p</i> &lt; 0.05), suggesting that middle ear changes contribute to the observed DP amplitude reduction. Our findings suggest that propofol maintains more stable cochlear amplifier responses, with lower inter-individual variability than isoflurane, making it a more suitable anesthetic regimen for longitudinal auditory monitoring in porcine models.</p>