Objective: To investigate the clinical application effect of vein arterialization in large-area skin flap transplantation. Methods: Sixty patients who were admitted to Xinsteel Center Hospital from September 2021 to September 2024 due to limb injury and required skin flap transplantation were selected as the study subjects. Using the random number table method, they were assigned to two groups. The control group underwent conventional skin flap transplantation, while the experimental group received vein arterialization on this basis. Comparisons were made between the two groups on perioperative indicators (surgery time and intraoperative blood loss), hospital stay, incidence rates of vascular crisis after 2 weeks, 1 month, and 6 months of postoperative follow-up, and the condition of skin flaps (incidence and area of skin flap necrosis). Results: Compared with the control group, the experimental group showed a significant increase in surgery time and a significant reduction in hospital stay (P<0.05). Intraoperative blood loss of the two groups was similar (P>0.05). After 2 weeks and 1 month of postoperative follow-up, the incidence rates of vascular crisis and flap necrosis, and area of flap necrosis in the experimental group were significantly lower and smaller (P<0.05). At 6 months after surgery, the incidence rates of vascular crisis and flap necrosis, and area of flap necrosis in the experimental group were slightly lower and smaller, without statistically significant difference between the groups (P>0.05). Conclusion: Although vein arterialization extends the duration of skin flap transplantation to a certain extent, it can effectively reduce the incidence rates of vascular crisis and skin flap necrosis in the early stage after surgery, reduce the area of skin flap necrosis, and dose not increase intraoperative blood loss, significantly promoting postoperative recovery.