Background: Intestinal failure is a chronic condition related to loss of bowel length and/or function, resulting in dependence on central venous catheters for fluids and nutrition. Catheter use can be associated with significant complications, including catheter‐related bloodstream infections (CRBSIs), which can lead to loss of vascular access, advancing intestinal failure associated–liver disease and death. Our objective was to evaluate the effectiveness and safety of ethanol locks as compared with standard heparin locks in pediatric intestinal failure. Methods: Databases, including MEDLINE and EMBASE, were searched until March 2017. Titles and abstracts were reviewed independently and relevant articles reassessed by full‐text review. The main outcome was the rate of CRBSIs, while secondary outcomes were catheter replacement and repair. Results: Nine observational studies were included. The mean difference in rate of CRBSIs was 6.27 per 1000 catheter days (95% CI, 4.89–7.66) favoring ethanol locks, with a 63% overall reduction in infection rate. The mean difference in catheter replacement rate (per 1000 catheter days) was 4.56 (95% Cl, 2.68–6.43) favoring ethanol locks. The overall effect on catheter repair rate (per 1000 catheter days) was −1.67 (95% CI, −2.30 to −1.05), indicating lower repair rate with heparin locks. Conclusion: Sufficient evidence was noted showing that ethanol locks reduced CRBSIs and catheter replacements. Our findings raise questions about the effect of the ethanol lock on catheter integrity based on the noted increase in repair rate. This requires further prospective evaluation and may support selective application of ethanol locks to patients with documented CRBSIs.