AIM: To determine the earliest time point at which anastomotic leaks can be detected in patients undergoing total colectomy (TC) with primary ileorectal anastomosis (IRA) for Familial Adenomatous Polyposis (FAP). METHOD: A case-controlled study of 10 anastomotic leak patients versus 20 controls following laparoscopic TC with IRA for FAP (from 96 consecutive patients between 2006-2013). Panel time-series data regression was performed using a double subscript structure to include both variables. A generalized least squares multi-variate approach was applied in a random effects setting to calculate correlations for observations, with anastomotic leak being the dependent variable. Univariate and multivariate regression calculations were then performed according to individual observations at each recorded time point. Time-series analysis was used to determine when a variable became significant in the leak group. RESULTS: Multivariate analysis identified a significant difference between leak and control groups in mean heart rate (p=<0.001), mean respiratory rate (p=0.017), and mean urine output (p=0.001). Time-point analysis showed that heart rate was significantly different between leak and control groups at post-operative day 4.25. Multivariate analysis identified a significant difference between groups in ALT (p=0.006), Bilirubin (p=0.008), Creatinine (p=0.001), Haemoglobin (p=<0.001), and Urea (p=0.007). There were no differences between groups with regards to markers of inflammation such as albumin, white blood cell count, neutrophil count, and CRP. CONCLUSION: Anastomotic leaks can be detected early (within 4.5 days of surgery) through changes in physiological, blood test, and observational parameters, providing an opportunity for early intervention in these patients to salvage the anastomosis. This article is protected by copyright. All rights reserved.