Experimental data about the efficacy and safety of sealing devices are rare. Therefore, this study investigated these parameters for three commercially available energy-based vascular sealing and cutting systems. In male hybrid pigs, 487 carotid artery segments were sealed and cut using the harmonic scalpel or several bipolar sealing devices. The sealing failure rate, burst pressure, process time, and extent of lateral thermal damage were analyzed. A regular sealing and cutting process in more than 90% of the carotid arteries was found using the following instruments: LS1520, ACE (level 1), ACE (level 3), CS14C (level 1), WAVE (level 1), and WAVE (level 5). The largest failure rate was found for the CS14C device (level 5: initial sealing failure, 21.5%). The maximal mean burst pressure (1727 ± 453 mmHg) was reached using the ACE device (level 1). Significant differences were found in the size of the lateral thermal damage, which a ranged from 2.5 mm (LS1520) to 1.51 mm (CS14C, level 1). The process time ranged widely from 6.8 s (ACE, level 5) to 31.83 s (WAVE, level 1). The current study demonstrated that all the tested devices are efficacious and safe in sealing and cutting arteries up to 5 mm in diameter. All the devices showed supraphysiologic mean burst pressures. Differences in failure rate, thermal damage, and process time lead to an advised application of the different systems.