Background and Aims Destructive wounds in the extremities often involve damage to major blood vessels. If not properly managed, they can lead to severe consequences such as limb ischemic necrosis and amputation. In order to explore diagnostic and treatment methods for such destructive wounds, this study was performed on the clinical outcomes of using free flaps combined with vascular reconstruction to repair upper limb destructive wounds combined with major vascular injuries to provide reference and guidance for the clinical treatment of such destructive wounds.Methods A retrospective analysis was conducted on 45 patients with upper limb destructive wounds and significant vascular injuries who underwent repair using free flaps combined with vascular reconstruction at Beijing Jishuitan Hospital from December 2017 to December 2022. The evaluation and treatment methods for vascular injuries, types of free flaps used for wound repair, postoperative vascular patency and limb perfusion, flap survival, and wound and donor site healing were summarized. During the last follow-up, hand muscle and nerve repair assessment criteria from the Hand Surgery Society of the Chinese Medical Association were used to evaluate the muscle strength of hand flexion and extension and finger sensory function.Results Among the 45 patients, there were 38 males and 7 females, with a mean age of (39.4±15.1) years. Five cases involved upper arm destructive wounds combined with brachial artery injuries, and 40 cases involved forearm and wrist destructive wounds combined with radial and/or ulnar artery injuries. The reconstruction methods included significant saphenous vein bridge reconstruction of the brachial artery in 3 cases (6.7%), artificial vascular bridge reconstruction of the brachial artery in 2 cases (4.4%), significant saphenous vein bridge reconstruction of the ulnar artery in 1 case (2.2%), significant saphenous vein bridge reconstruction of the radial artery in 35 cases (77.8%), and blood flow bridge flap reconstruction of the radial artery in 4 cases (8.9%). Anterolateral thigh flaps were used in 29 cases (64.4%), paraumbilical perforator flaps in 12 cases (26.7%), groin flaps in 1 case (2.2%), and latissimus dorsi muscle flaps (with an area of 24-10 cm×35-18 cm) in 3 cases (6.7%). The donor site was directly sutured and closed in 24 cases (53.3%), nearby flaps were transferred for coverage in 13 cases (28.9%), and split-thickness skin grafts were used for coverage in 8 cases (17.8%). The survival rate of free flaps was 97.8% (44/45), and the wound healing rate at stage I was 93.3% (42/45). Thirty-eight patients were followed up for 3-36 months, and the flaps and limb perfusion were satisfactory. The patency rate of reconstructed vessels was 92.1% (35/38). The patient's thumb and finger extension function was normal at the last follow-up. The muscle strength assessment of thumb and finger flexion showed grade Ⅴ in 5 cases (13.2%), grade Ⅳ in 13 cases (34.2%), grade Ⅲ in 16 cases (42.1%), and grade Ⅱ in 4 cases (10.5%). The finger sensory function assessment showed grade S4 in 5 cases (13.2%), grade S3 in 10 cases (26.3%), grade S2 in 12 cases (31.6%), grade S1 in 8 cases (21.0%), and grade S0 in 3 cases (7.9%).Conclusion Prompt evaluation and treatment of vascular injuries are necessary for upper limb destructive wounds combined with major vascular injuries. Autogenous or artificial vascular reconstruction should be performed based on the diameter of the injured vessels to prevent limb ischemic necrosis. Reconstructed vessels and destructive wounds should be covered promptly with tissue flaps rich in blood supply. Free flap transplantation should be prioritized whenever possible as it yields better results than distal pedicle flap transplantation.