This study is a retrospective review of 122 patients who underwent single-level lumbar spine fusion. The objectives were to directly compare perioperative morbidity and early results of single-level anterior interbody versus posterolateral intertransverse process lumbar spine fusion and to provide objective findings that may be useful in selecting surgical method. Lumbar spinal fusion is a well-recognized surgical treatment of intractable low back pain resulting from DDD or spondylolisthesis. Assessments of techniques, results, and outcomes have been published, but detailed head-to-head comparisons of anterior versus posterior approaches with objective operative and postoperative data are not available in the literature. A retrospective review of 122 patients who underwent either an anterior interbody or posterolateral intertransverse process (average follow-up 22 and 26 months, respectively) single-level instrumented lumbar spinal fusion was performed. Surgical, perioperative, and follow-up data were obtained directly from medical records. The findings compared included estimated blood loss, need for blood transfusion, number of units transfused, operative time, number of days in hospital, need for transitional facility care, complications, need for further surgery, radiographic fusion, and clinical results. There was significantly less blood loss, need for transfusion, amount of blood transfused, operative time, and hospital stay for patients with anterior fusion procedures (p < 0.01). There was no significant difference in need for transitional facility care, complication rates, and given follow-up period in radiographic fusion rate and clinical outcome. Clinical results were significantly worse for those undergoing revision versus primary fusion (p < 0.01). The anterior approach to single-level lumbar fusion is associated with less morbidity than the posterolateral approach. This may in turn affect surgical outcome and hospital cost. However, both approaches to single-level lumbar fusion produce similar early fusion rates and clinical results. Revision fusions had poor early results regardless of approach.