Background Clinical effectiveness and safety of biological and synthetic adhesives in digestive closures have been evaluated. Their use is becoming more prevalent, as rigidity and inflexibility are its more remarkable weaknesses. However, little is known about their role in gastric and anastomotic closures. Moreover, usefulness of novel flexible types of synthetic adhesives as n-butyl-cyanoacrylate has not been assessed yet. Materials and Methods One centimeter long gastrotomy was performed in 24 male Wistar rats, which were divided depending on the type of closure method employed: manual USP 5/0 silk interrupted suture versus sutureless closure with Histoacryl Flexible (n-butyl-cyanoacrylate with softener) or Histoacryl Double Component (n-butyl-cyanoacrylate with softener and hardener). Microscopic evaluation of the suture viability and integrity was performed, and adhesion formation during the cicatrization process were assessed. During an 8-week follow-up clinical and histopathological aspects as well as hematologic and inflammatory biomarkers were studied. Results No differences among groups where found in any of the clinical, analytical, or histopathological issues assessed except for a higher incidence rate of adhesions in the Histoacryl Double Component group when compared with hand-sewn suture group (P = .04). Our results support experimental studies in large mammals (pigs) for further study of sutureless hollow viscera closure.