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Background: In colorectal surgery, anastomotic leakage (AL) is the most significant complication. Sealants applied around the colon anastomosis may help prevent AL by giving the anastomosis time to heal by mechanically supporting the anastomosis and preventing bacteria leaking into the peritoneal cavity. The aim of this study is to compare commercially available sealants on their efficacy of preventing leakage in a validated mouse model for AL., Methods: Six sealants (Evicel, Omnex, VascuSeal, PleuraSeal, BioGlue, and Colle Chirurgicale Cardial) were applied around an anastomosis constructed with five interrupted sutures in mice, and compared with a control group without sealant. Outcome measures were AL, anastomotic bursting pressure, and death., Results: In the control group there was a 40% death rate with a 50% rate of AL. None of the sealants were able to diminish the rate of AL. Furthermore, use of the majority of sealants resulted in failure to thrive, increased rates of ileus, and higher mortality rates., Conclusions: If sealing of a colorectal anastomosis could achieve a reduction of incidence of clinical AL, this would be a promising tool for prevention of leakage in colorectal surgery. In this study, we found no evidence that sealants reduce leakage rates in a mouse model for AL. However, the negative results of this study make us emphasize the need of systemic research, investigating histologic tissue reaction of the bowel to different sealants, the capacity of sealants to form a watertight barrier, their time of degradation, and finally their results in large animal models for AL., (Copyright © 2013 Elsevier Inc. All rights reserved.)