Recent studies have demonstrated excellent results in treating isthmic spondylolisthesis via an anterior lumbar interbody fusion (ALIF). The authors describe 3 patients with isthmic spondylolisthesis at L5-S1 who experienced sacral fractures after insertion of a unique, stand-alone anterior interbody fixation device. Three consecutive patients at a single institution were treated for Grade I spondylolisthesis at L5-S1 via a standalone ALIF with insertion of a novel biomechanical interbody device. This device is made of polyetheretherketone and has an integrated system for internal fixation into the vertebral bodies. In each patient a bone morphogenetic protein-soaked sponge was placed for the fusion. The indications for treatment in each patient were back and radicular pain that had been unsuccessfully treated with conservative measures. All 3 patients had reduction of their spondylolisthesis and resolution of their unilateral radiculopathies immediately postoperatively. Within 1 month of surgery, all 3 patients had failure of the device and recurrence of their symptoms. In each case the failure was due to fracture of the anterior portion of the S-1 body. Each patient underwent reduction and pedicle screw fixation at L5-S1. In all cases, there was successful reduction in their recurrent spondylolisthesis and resolution of their radiculopathies. Treatment of Grade I isthmic spondylolisthesis at L5-S1 with stand-alone ALIF and fixation can lead to sacral fracture from high stress loads at that level in the spine, and consideration should be made either for supplemental pedicle screw fixation or a completely posterior approach.