ObjectiveThis paper intends to evaluate the association between Down Syndrome (DS) and postoperative medical and surgical complications and inpatient postoperative mortality in pediatric patients undergoing intestinal operations. MethodsThe 2012 Kids' Inpatient Database was queried to compare short-term postoperative medical and surgical complications and in-patient mortality among patients with DS undergoing intestinal operations to a cohort without DS using inverse probability weighting. Subset analysis was performed for patients undergoing intestinal operations exclusive of gastrostomy placement. Adverse treatment effects were calculated for the outcomes of interest. ResultsOf 17,026 pediatric patients undergoing intestinal operations, 444 had DS. In unadjusted analysis, medical complications (urinary tract infection, deep venous thrombosis, sepsis, pneumonia) occurred in 7.9% of patients with DS, compared to 14.1% of those without (p < 0.001). Surgical complications (wound disruption, hemorrhage, superficial or deep wound infection) occurred in 3.5% of patients with DS, compared to 4.6% of those without (p = 0.34), and in-patient mortality occurred in 0.3% of patients with DS, compared to 2.7% of those without (p = 0.009). Adverse treatment effects (ATE) calculated after inverse probability weighting demonstrated no difference for medical or surgical complications but a significantly decreased mortality with DS. ConclusionsContrary to common perception and data extrapolated from the adult literature, pediatric patients with DS have neither higher medical nor surgical complication rates after intestinal operations. Similar to patients undergoing congenital heart surgery, pediatric patients with DS have a lower postoperative inpatient mortality after these general operations compared to those without DS. Mechanisms influencing risks in DS patient remain unknown. Level of EvidenceLevel III, retrospective comparative study.