Recombinant human bone morphogenetic protein–2 (rhBMP-2) promotes the induction of bone growth and is widely used in spine surgery to enhance arthrodesis. Recombinant human BMP-2 has been associated with a variety of complications including ectopic bone formation, adjacent-level fusion, local bone resorption, osteolysis, and radiculitis. Some of the complications associated with rhBMP-2 may be the result of rhBMP-2 induction of the inflammatory host response. In this paper the authors report on a patient with prior transforaminal lumbar interbody fusion (TLIF) using an interbody cage packed with rhBMP-2, in which rhBMP-2 possibly contributed to vascular injury during an attempted anterior lumbar interbody fusion. This 63-year-old man presented with a 1-year history of worsening refractory low-back pain and radiculopathy caused by a Grade 1 spondylolisthesis at L4–5. He underwent an uncomplicated L4–5 TLIF using an rhBMP-2–packed interbody cage. Postoperatively, he experienced marginal improvement of his symptoms. Within the next year and a half the patient returned with unremitting low-back pain and neurogenic claudication that failed to respond to conservative measures. Radiological imaging of the patient revealed screw loosening and pseudarthrosis. He underwent an anterior retroperitoneal approach with a plan for removal of the previous cage, complete discectomy, and placement of a femoral ring. During the retroperitoneal approach the iliac vein was adhered with scarring and fibrosis to the underlying previously operated L4–5 interbody space. During mobilization the left iliac vein was torn, resulting in significant blood loss and cardiac arrest requiring chest compression, defibrillator shocks, and blood transfusion. The patient was stabilized, the operation was terminated, and he was transferred to the intensive care unit. He recovered over the next several days and was discharged at his neurological baseline. The authors propose that the rhBMP-2–induced host inflammatory response partially contributed to vessel fibrosis and scarring, resulting in the life-threatening vascular injury during the reoperation. Spine surgeons should be aware of this potential inflammatory fibrosis in addition to other reported complications related to rhBMP-2.