A novel device was designed to assist with microvascular arterial anastomoses. This study compares the safety and efficacy of the anastomosis-assisting device with manual suturing in an ovine model. Arteries with a diameter ranging from 2 to 4mm were transected and anastomosed at four locations. A comparison was done between manual anastomoses and anastomoses performed with a novel anastomotic device in seven sheep. All the device-assisted anastomoses were performed by a single surgeon. At day 45±7, anastomotic sites were dissected to determine patency, and samples were obtained for pathology. Thirteen of 13 (100%) samples from the Vesseal™ group demonstrated patency both on the day the anastomoses were performed and after the 45-day follow-up period. All four additional anastomoses performed using the Vesseal™ were found patent. In the hand-suturing group, six of six (100%) samples demonstrated patency on the day of the anastomoses and five of six (83%) were patent after the follow-up period. No thromboses or adverse events were observed in the anastomoses in either group. No difference in histopathology of the anastomoses was observed between the groups. The anastomosis-assisting device is a safe and efficacious alternative to hand suturing. The patency rates of device-assisted anastomoses were greater than those of manual suturing and pose no additional risk, as demonstrated by clinical observation, histopathology, and macroscopic evaluation. The Vesseal™ anastomosis-assisting device may be a viable alternative to manual suturing, with an ergonomic and intuitive design, short learning curve, and consistent results.