Open saphenous vein harvesting can be associated with wound complications, incision pain, prolonged convalescence, and poor cosmetic results. Endoscopic vein harvesting has been widely used for prevention of these problems. We compared outcomes of open and endoscopic vein harvesting for coronary artery bypass grafting at the Texas Heart Institute. We retrospectively analyzed data from 1,573 consecutive coronary artery bypass procedures performed at our institution during a 20-month period. Each procedure included saphenectomy by endoscopic vein harvesting (n = 588) performed by physician assistants, or by traditional open vein harvesting (n = 985) performed by physicians or physician assistants. The primary outcome variable was the incidence of postoperative leg infections. Both groups were similar in terms of preoperative risk factors. After surgery, leg wound infections were significantly less frequent in the endoscopic vein harvesting group (3/588, 0.5%) than in the open vein harvesting group (27/985, 2.7%; P < 0.002). The most common organism involved in leg infections was Staphylococcus (20/30, 66%): S. aureus was present in 14 of 30 infections (47%). Open vein harvesting was the only significant independent risk factor for leg infection. We conclude that endoscopic vein harvesting reduces leg wound infections, is safe and reliable, and should be the standard of care when venous conduits are required for coronary artery bypass grafting and vascular procedures. Although the transition from open to endoscopic vein harvesting can be challenging in institutions, it can be successful if operators receive adequate training in endoscopic technique and are supported by surgeons and staff.