68 patients with two-level degenerative lumbar disorders were randomized to receive treatment with unilateral or bilateral transforaminal lumbar interbody fusion (TLIF). Perioperative, clinical and radiographic outcomes were assessed and compared. Patients who received unilateral TLIF experienced less blood loss, shorter operative times, and had lower implant costs. Outcomes of leg and back pain, disability, health-related quality of life, radiographic fusion, and complication rate were comparable after 2 years. Results suggest unilateral TLIF as a safe and effective alternative to bilateral TLIF.