Purpose <p>Esophageal anastomotic leaks (AL) and perforations in children are associated with significant morbidity, and early recognition remains challenging. We evaluated postoperative drain fluid amylase levels in children with and without esophageal leaks to explore its potential role as an adjunctive marker of clinically significant injury.</p> Methods <p>Single-institution retrospective study of children (0–18 years) undergoing esophageal surgery with postoperative drain fluid amylase testing (March 2023–October 2025). Patients were categorized based on the presence or absence of clinically or radiographically confirmed leak. Peak amylase values were analyzed by leak type (contained vs. uncontained).</p> Results <p> Seventy-five children were included, 64 without leak and 11 with anastomotic leak (<i>n</i> = 8) or perforation (<i>n</i> = 3). Median peak drain fluid amylase was 20 U/L (IQR 11–48) in children without a leak. Contained leaks demonstrated similarly low values (23.5 U/L [IQR 13–25.5]), whereas uncontained leaks and perforations showed markedly elevated levels (median 3423 U/L [IQR 1,776–4,026]). In one patient, amylase elevation preceded clinical deterioration by 24&#xa0;h.</p> Conclusion <p>Postoperative drain fluid amylase was elevated in clinically significant uncontained esophageal leaks and perforations but not in contained leaks. These findings suggest that drain fluid amylase may serve as an adjunctive marker of uncontained esophageal leaks in selected patients with drains in place. Prospective validation is required.</p>