Background: Laparoscopic intracorporeal suturing and knot tying for anastomosis are considered the most difficult laparoscopic skills to master. The aim of this study was to establish the safety and efficacy of barbed suture for intestinal sutures to close the gastrojejunal anastomosis in obese patients undergoing gastric bypass. Study Design: All consecutive patients undergoing gastric bypass were screened for enrollment in our study. Patients were randomly allocated to undergo knotless anastomosis with barbed suture (V-Loc™ 180; Covidien, Mansfield, MA) (case group) or knot-tying anastomosis with 3/0 polyglactin sutures (Polysorb^®; Covidien) (control group). The primary outcome was the time needed for the gastrojejunal anastomosis and the operative time. The secondary outcomes were the incidence of leak, bleeding, and stenosis and the evaluation of the cost of the different procedures evaluated. Results: Among the 60 consecutive patients enrolled in our study, 30 underwent knot-tying anastomosis, and 30 underwent knotless anastomosis. The time needed for the anastomosis was significantly less (P<.001) in the knotless group, whereas no significant differences were found between the two groups for operative time (P=.151). We recorded one leak in the control group and one leak in the case group (P=1.000). One bleeding in the case group (P=1.000) and no stenosis in either group was recorded. Finally, in our experience, the knotless anastomosis was cheaper than the knot-tying anastomosis (P<.001). Conclusions: Our study appears to be encouraging to suggest the use of barbed suture for gastrointestinal anastomosis.