Simple Summary The assessment of the depth of anesthesia in pigs is challenging. The nociceptive withdrawal reflex is a physiological, polysynaptic spinal reflex occurring in response to noxious stimulations, and the tracking of its thresholds has been shown to be possibly useful in evaluating the depth of anesthesia. In the present study, we investigated how increasing the dose of the anesthetic drug propofol influences the nociceptive withdrawal reflex thresholds in pigs. The nociceptive withdrawal reflex thresholds were continuously recorded while increasing the dose of propofol that was administered. Each animal underwent the same experimental protocol on three different days. We found that the nociceptive withdrawal reflex thresholds increased with an increasing dose of propofol, and that the same trend was present on the three experimental days. Our results suggest that the assessment of the nociceptive withdrawal reflex thresholds may complement the depth of anesthesia evaluation in pigs receiving propofol.Abstract The nociceptive withdrawal reflex (NWR) is a physiological, polysynaptic spinal reflex occurring in response to noxious stimulations. Continuous NWR threshold (NWRt) tracking has been shown to be possibly useful in the depth of anesthesia assessment. The primary aim of this study was to describe how propofol modulates the NWRt over time in pigs. Five juvenile pigs (anesthetized three times) were included. An intravenous (IV) infusion of propofol (20 mg/kg/h) was started, and boli were administered to effect until intubation. Afterwards, the infusion was increased every ten minutes by 6 mg/kg/h, together with an IV bolus of 0.5 mg/kg, until reaching an electroencephalographic suppression ratio (SR) of between 10% and 30%. The NWRt was continuously monitored. For data analysis, the time span between 15 min following intubation and the end of propofol infusion was considered. Individual durations of propofol administration were divided into five equal time intervals for each pig (TI1-TI5). A linear regression between NWRt and TI was performed for each pig. Moreover, the baseline NWRt and slopes of the linear regression (b1) were compared among days using a Friedman Repeated Measures Analysis of Variance on Ranks. The NWRt always increased with the propofol dose (b1 = 4.71 +/- 3.23; mean +/- standard deviation). No significant differences were found between the baseline NWRt and the b1 values. Our results suggest that the NWRt may complement the depth of anesthesia assessment in pigs receiving propofol.