Objective:To investigate the diagnostic value of ultrasound contrast agent enema (UCAE) for anastomotic leakage (AL) after rectal cancer surgery.Methods:From January 2020 to December 2022, a total of 95 patients with presacral fluid collection after rectal cancer surgery in the Sixth Affiliated Hospital of Sun Yat-sen University who received perineal ultrasound (PNUS) and UCAE were retrospectively selected. Among them, 70 patients (73.3%) were diagnosed with AL.After PNUS scanning, all patients received a diluted ultrasound contrast agent administered through the rectum. Receiver operating characteristic (ROC) curve were used to compare the accuracies of PNUS, UCAE, CT, MRI and water-soluble contrast enema in the diagnosis of AL. Factors that may have impacts on the sensitivity of UCAE were thoroughly analyzed.Results:UCAE improved the consistency (Kappa value: 0.757 vs 0.292, P<0.001) and accuracy (AUC: 0.893 vs 0.693, P<0.001) of PNUS in the diagnosis of AL, and its diagnostic accuracy was comparable to that of CT (AUC 0.807), MRI (AUC 0.811) and water-soluble contrast enema (AUC 0.923) (all P>0.05). For mid-to-high AL (anastomotic stoma distance ≥70 mm) and tiny AL (≤3 mm), the sensitivity of UCAE decreased significantly (anastomotic stoma position: 25.0% vs 85.5%, P=0.001; anastomotic leak diameter: 42.9% vs 87.5%, P=0.002). Conclusions:UCAE can significantly improve the diagnostic accuracy and consistency of PNUS for AL after rectal cancer surgery, and its diagnostic sensitivity is affected by the anastomotic stoma distance and the diameter of the leak.