Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. An application of VEGF may enhance angiogenesis in the grafted tendon in anterior cruciate ligament (ACL) reconstruction, and the application may affect mechanical characteristics of the ACL graft. Controlled laboratory study. Eighteen sheep were divided into groups I and II. In group I, the harvested semitendinosus tendon was soaked in VEGF solution, and the right knee then underwent ACL reconstruction using this tendon. In group II, the right knee underwent identical procedures to those of group I except that the harvested tendon was soaked in phosphate-buffered saline. All animals were sacrificed 12 weeks after ACL reconstruction. Histologic findings showed that newly formed vessels and infiltrative fibroblasts were more abundant in group I than in group II. The anterior-posterior translation of the knee during an anterior-posterior force of +/- 100 N was significantly larger in group I than in group II by 2.58 mm (95% confidence interval, -1.76 mm to 1.76 mm) (P = .002). The linear stiffness of the femur-graft-tibia complex in group I was significantly lower than that in group II by 41.5 N/mm (95% confidence interval, -32.2 N/mm to 32.2 N/mm) (P = .017). This study has revealed that VEGF as administered in this study promotes angiogenesis in the ACL graft and significantly reduces the stiffness of the ACL graft with increased knee laxity at 12 weeks after ACL reconstruction. Exogenous VEGF application for ACL reconstruction can induce an increase in knee laxity and a decrease in the stiffness of the grafted tendon at least temporarily after ACL reconstruction. These potentially negative mechanical effects need to be taken into account when considering clinical use of VEGF.