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BACKGROUND Enhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, ERAS has not been reported in neonatal surgery. The present prospective study explored the application value of ERAS in treating congenital duodenal obstruction (CDO). METHODS A total of 68 cases of CDO were collected from October 1, 2017 to July 31, 2019. We divided patients with a prenatal diagnosis of congenital duodenal obstruction into the ERAS group and those who were diagnosed the disease after birth into the control group. The ERAS group adopted ERAS-related measures, and the control group followed the usual measures. The study compared the differences in the gestational age, birth weight, length of hospital stay (LOS), complications, feeding intolerance, and weight one month after surgery between the two groups. RESULTS A total of 49 patients were included in the analysis, including 23 who were allocated to the ERAS group and 26 to the control group. The LOS was 9.696±1.222 days in the ERAS group and 12.654±1.686 days in the control group, resulting in a significantly shorter LOS in the ERAS group than in the control group (p<0.001). One month after surgery, the neonates in the ERAS group weighted significantly more than those in the control group. No differences were observed in birth weight, gestational age, and the incidence of complications or feeding intolerance between the two groups. CONCLUSION In this single-center study, the implementation of neonate-specific ERAS for CDO surgery was feasible and safe and led to a shorter LOS without increasing the incidence of complications or feeding intolerance. TYPE OF STUDY Treatment Study LEVEL OF EVIDENCE: Level III.