Purpose: Malnutrition is a common feature in critically ill children. Enteral nutrition (EN) is the main strategy to nutritionally support critical ill children, but its use can be hindered by the development of intolerance. The study aimed to assess the effectiveness and safety of amoxicillin/clavulanate (A/C) to treat EN intolerance. Methods: We retrospectively evaluated patients admitted to the pediatric intensive care unit from October 2018 to October 2019. We conducted a case-control study: in the first 6 months (October 2018-April 2019) we implemented the nutritional protocol of our Institution with no drug, whereas in the second half (May 2019-October 2019) we employed A/C for 1 week at a dose of 10 mg/kg twice daily. Results: Twelve cases were compared with 12 controls. At the final evaluation, enteral intake was significantly higher than that at baseline in the cases (from 2.1±3.7 to 66.1±27.4% of requirement, p=0.0001 by Wilcoxon matched-pairs signed rank test) but not in the controls (from 0.2±0.8 to 6.0±14.1% of the requirement, p=NS). Final gastric residual volume at the end of the observation was significantly lower in the cases than in the controls (p=0.0398). The drug was well tolerated as shown by the similar safety outcomes in both cases and controls. Conclusion Malnutrition exposes critically ill children to several complications that affect the severity of disease course, length of stay, and mortality; all may be prevented by early EN. The development of intolerance to EN could be addressed with the use of A/C. Future prospective clinical trials are needed to confirm these conclusions.