Background: CT imaging is the primary diagnostic approach to assess the integrity of the intrathoracic anastomosis following Ivor Lewis esophagectomy. In the postoperative setting interpretation of CT findings, such as air and fluid collections, may be challenging. Establishment of a scoring system that incorporates CT findings to diagnose anastomotic leakage could assist radiologists and surgeons in the postoperative phase. Methods: Consecutive patients who underwent a CT scan for a clinical suspicion of postoperative anastomotic leakage following Ivor Lewis esophagectomy between 2010 and 2016 in two medical centers were retrospectively included. Scans were excluded when oral contrast was not (correctly) administered. Acquired images were randomized and independently assessed by two experienced gastrointestinal radiologists, blinded for clinical information. For this study anastomotic leakage was defined as a visible defect during endoscopy or thoracotomy. Results: A total of 80 patients had 101 CT scans, resulting in 32 scans with a confirmed anastomotic leak (25 patients). After multivariable backward stepwise logistic regression, a practical 5-point scoring system was developed, which included the following CT findings: presence of extraluminal oral contrast, air collection at the anastomotic site, fluid collection at the anastomotic site, pneumothorax and loculated pleural effusion. Patients with a score of ≥3 were considered at high risk for anastomotic leakage (positive predictive value: 83.3%), patients with scores <3 were considered at low risk for anastomotic leakage (negative predictive value: 84.4%). The scoring system showed a superior diagnostic performance compared to the original CT report and blinded interpretation of two radiologists. Conclusions: Our CT-based practical scoring system enables a standardized approach in CT assessment and could facilitate early recognition of anastomotic leakage in patients after Ivor Lewis esophagectomy.