Purpose: Anastomotic leakage (AL) is the anathema of colorectal surgery. Its occurrence leads to increased morbidity and mortality and a prolonged hospital stay. Much work has gone into studying various biomarkers in drain fluid to facilitate early detection of AL. This stage 2a development study aims to assess the safety and feasibility of reliably detecting the iodine in Gastrografin (GG; Bayer Australia Ltd.) in drain fluid and stool samples by dual-energy computed tomography (DECT). Methods: This is a prospective, observational, controlled, consecutive cohort study establishing the safety and feasibility of the detection of GG in surgical drain fluid and stool as a biomarker of AL when patients with a low pelvic colorectal anastomosis undergo luminal flushing of the rectal tube with GG. Results: Ten consecutive patients were allocated to the saline flush group and the following 10 to the GG flush group. Three patients in the saline flush group developed an AL. One patient in the GG flush group developed an AL. An elevation in the drain fluid GG was detected using DECT on the day of clinical deterioration. None of the patients in the control group were found to have a positive result on DECT. Conclusion This study demonstrates the safety of a novel approach to the early detection of AL from extraperitoneal colorectal anastomoses. The technique requires validation in a larger cohort and a multicenter study is planned to investigate the efficacy of GG rectal tube flushes as an early biomarker of AL in low pelvic anastomoses.