Vessel sealing devices effectively produce hemostatic seals with minimal thermal damage, but the strength of seals decreases as vessel diameter increases. Because vessels sealed at an angle to the vessel require a greater functional seal diameter than those sealed perpendicularly to the vessel, it was hypothesized that perpendicular seals would have comparably higher burst pressures. Ex vivo, porcine carotid arteries of nominal diameters of 5, 6, and 7 mm were sealed perpendicularly to and at a 45° angle to the longitudinal axis of the vessels, and burst pressures of the sealed vessels were measured. Overall burst pressures were 51% greater for perpendicular seals than for angled seals (P<.001). Mean burst pressures for the 5-mm angled and 7-mm perpendicular groups, which have similar seal lengths, were not significantly different (P=.959). Analysis using the functional diameter as a covariate indicated that the seal length is the primary variable in determining burst pressure, and not some other inherent characteristic of angled versus perpendicular sealing. These results suggest that at least for vessels ≥5 mm in diameter, surgeons should approach vessels perpendicularly and not at an angle, for the highest possible seal strength. The development of articulated sealing and cutting devices would provide greater seal strength, in addition to improved maneuverability, especially in laparoscopic surgery, where angles of approach may be limited by the fixed location of surface cannulas.