Background <p>Flexible endoscopic suturing tools are complex and may have a long learning curve. This porcine study evaluated the safety and performance of a simplified suturing system compared with a commercially available device for the repair of gastrointestinal mucosal defects.</p> Methods <p>This IACUC-approved study included four healthy swine. A total of ten defects (six in the stomach and four in the rectosigmoid colon) were created in each animal. Defects were randomly assigned to closure with either the novel or the commercially available system using a therapeutic gastroscope. Technical success was defined as mucosal closure of the defect with the inability to visualize any significant portion of the resection bed. Additional performance metrics included procedure time and device ease of use (assessed using the NASA Task Load Index [TLI]) and adverse events.</p> Results <p>No adverse events were reported post-procedurally for any of the test animals. The proportion of target resection sites achieving technical success was 100% in both treatment groups. The mean SimpleStitch NASA-TLI score was lower compared to the OverStitch device. Closure times were similar between the two devices. Histological assessment scores indicated expected healing response without evidence of perforation, leakage, or abscess formation.</p> Conclusion <p>A novel full-thickness suturing system safely and effectively closed mucosal defects. Lower NASA-TLI scores suggest that the novel suturing device may offer simpler, less demanding use compared to the predicate device, potentially reducing the learning curve for endoscopic suturing procedures.</p>