A vessel harvesting system that is suitable for harvesting target vessels such as the saphenous vein or radial artery for cardiac artery bypass graft surgery. The system includes a vessel harvesting tool with an elongated cannula and a plurality of surgical instruments therein for separating the target vessels from the surrounding tissue and side branches. The harvesting tool includes a modular handle unit with a base attached to the elongated cannula and a sled that can adapt the base to various types of vessel severing/securing tools, such as tissue welders, bipolar scissors, and bipolar bisectors. The handle unit may be relatively rigid and integrated with the various tool movement controls to facilitate one-handed operation by a user. A severing/securing tool rotation mechanism may be incorporated within the handle and operated by a thumbwheel or other such mechanism. The vessel harvesting system may also provide distal CO2 insufflation for enhanced maintenance of the operating cavity.