PURPOSE: The effects of sufentanil-ropivacaine combination on the parturient women and the course of labor have been well documented. However, there is little information regarding the time-dependent pharmacokinetic characteristics of sufentanil after epidural administration in laboring women. We aimed to develop a population PK model for epidural sufentanil in laboring women to evaluate the sufentanil placental transfer quantitatively. PATIENTS AND METHODS: Forty-one participants who underwent epidural labor analgesia were recruited into this study. Patients received a continuous epidural infusion of sufentanil 0.3 µg/mL with ropivacaine 0.1%. Maternal venous blood samples and umbilical venous blood samples were collected for population PK analysis. The trends of sufentanil blood concentrations in the mothers and umbilical cord were predicted by the model. RESULTS: Sufentanil disposition after continuous epidural administration in laboring women followed a two-compartment pharmacokinetic model. The estimated sufentanil central clearance (CL), central volume of distribution (V1), clearance between central compartment and umbilical cord compartment (CL2), and umbilical cord volume of distribution (V2) were 176 L/h, 519 L, 0.0134 L/h, and 0.187 L. The absolute level of sufentanil in placental circulation is low after epidural administration. A slow decline in placental sufentanil concentration was predicted by the final PK model after epidural infusion was discontinued. CONCLUSION: A slow decline in placental sufentanil concentration is predicted by the final two-compartment PK model after epidural infusion was discontinued. This suggests that very large doses of epidural sufentanil should be avoided during labor analgesia. TRIAL REGISTRATION: https://www.chictr.org.cn, No: ChiCTR1800018810.