Background Endoscopic vein harvesting (EVH) is a widely accepted technique for coronary artery bypass grafting, with well-reported benefits. However, EVH is associated with severe hematoma formation at incision sites, resulting in postoperative pain. We hypothesized that the use of a leg wound drain at the incision site may reduce these comorbidities. Methods One hundred consecutive patients were prospectively randomly allocated into two groups of 50: group 1 with leg wound drains, and group 2 without drains. Group 1 patients underwent EVH followed by closure with a size 10 high vacuum leg wound drain (20 kPa), whereas group 2 underwent EVH followed by closure without a leg wound drain. Patients were assessed for postoperative pain, wound infection, and satisfaction using validated scoring systems immediately after surgery. Results Pain at rest (p < 0.001) and with movement (p < 0.001), incidence of hematoma (p < 0.001), and patient satisfaction (p < 0.001) were significantly improved in the drain group at days 1 to 7 and remained significant at week 6 after surgery. Interestingly, the use of antibiotics (6% versus 24%, p = 0.012) and the number of general practitioner visits (6% versus 26%, p = 0.012) were lower in the drain group compared with the no-drain group. However, there were no differences in the length of hospital stay between the two groups after surgery. Conclusions Our findings indicate that the use of a high vacuum leg drain after EVH for long saphenous vein is of clear therapeutic benefit in the early postoperative period. We also report that this technique may reduce antibiotic administration and general practitioner visits after patient discharge.