Lateral lumbar interbody fusion (LLIF) is a widely applied and useful procedure for spinal surgeries. However, posterior fixation has not yet been decided. We compared the radiographic and clinical outcomes of unilateral versus bilateral instrumented one-level LLIF for degenerative lumbar disease. We conducted a prospective cohort study of 100 patients, who underwent unilateral (group U) or bilateral (group B) instrumented one-level LLIF for degenerative lumbar disease. Forty-one patients in group U were undergoing unilateral pedicle screw instrumentation, and 59 patients in group B were undergoing bilateral pedicle screw instrumentation. Clinical characteristic and demographic data before surgery were compared. The intraoperative data, including operative time with changes in positions, intraoperative blood loss, and X-ray exposure time, as well as the perioperative data, including postoperative hospital stay and clinical and radiographic data were compared. As a result, Group U required a significantly shorter operating time than group B. The subsidence grade and fusion rates exhibited no significant differences in the postoperative radiographic evaluation. Group U had better results in clinical assessments than group B. However, group U required more additional surgeries owing to complications.