Instrumentation of the lumbosacral spine increasingly involves screw fixation to the sacrum. Recommended locations and techniques for screw placement vary, particularly when bicortical purchase of the sacrum is performed. The purpose of this study was to describe the critical anatomy and potential injuries to neurovascular and visceral structures anterior to the sacrum. Lack of awareness can lead to life-threatening complications. The study included 22 fresh human cadavers with no prior spinal surgery. Specimens were placed in a prone position, and the lumbosacral spine was exposed. Two 6.5-mm screws were inserted using one of two techniques, respectively: Starting just inferior to the S1 facet one screw was angled 25 degrees caudally and 30 degrees laterally; in the second technique, lateral inclination was increased to 45 degrees. In addition, all specimens had screws placed in the S2 pedicles. An anterior dissection was performed to allow evaluation of the neurovascular and visceral structures at risk for injury by, or adjacent to, the screw tips. All significant neurovascular structures in the area of concern were constant in position. The internal iliac vein and the lumbosacral nerve trunk were most at risk for injury by the 30 and 45 degrees laterally directed screws. The sigmoid colon, though close to the S2 screw, was protected by its mesentery. Screws placed in the S1 pedicle were least likely to injure the neurovascular bundle. A lateral and a midline safe zone were identified.