OBJECTIVE: To conduct a comparative analysis of the clinical efficacy and quality of life in elderly patients with lumbar degenerative disease (LDD) treated with TLIF (transforaminal lumbar interbody fusion) combined with either unilateral pedicle screw fixation (UPSF) or bilateral pedicle screw fixation (BPSF). METHODS: A total of 112 patients with single- or double-segment lumbar degenerative disease were divided into two groups. In the unilateral fixation cohort, 32 single-segment patients and 22 double-segment patients underwent TLIF combined with UPSF, whereas in the bilateral fixation cohort, 34 single-segment patients and 24 double-segment patients underwent TLIF combined with BPSF. Data on operative time, intraoperative blood loss, time to postoperative ambulation, length of hospital stay, and perioperative complications were collected and analysed. Pain and functional status were preoperatively evaluated, in addition to being postoperatively evaluated at 1, 6, and 12 months, using the visual analogue scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score, and Short Form-36 (SF-36) health survey questionnaire. Imaging follow-up was conducted for 1 year; at the final follow-up, the fusion rate was determined using the Bridwell fusion grading system, and clinical outcomes were assessed by using the modified MacNab criteria. RESULTS: All of the follow-up patients successfully completed the surgeries. There were no significant differences observed in average postoperative ambulation time or hospital stay between the UPSF and BPSF groups for either single- or double-segment patients. However, the UPSF group exhibited less average blood loss and a shorter surgery time (P < 0.05). At 12 months after surgery, there were no statistically significant differences observed in the VAS, ODI, or JOA scores between the UPSF and BPSF groups, although both scores were significantly improved compared with the preoperative scores. There were fewer perioperative complications observed in the UPSF group than in the BPSF group for both single-segment (P = 0.040) and double-segment (P = 0.009) patients. In terms of quality of life, the UPSF group exhibited better long-term physical and mental health outcomes compared with the BPSF group (single-segment PCS: preoperative, P = 0.694; 1 month, P = 0.310; 6 months, P = 0.022; 12 months, P = 0.020; MCS: preoperative, P = 0.849; 1 month, P = 0.655; 6 months, P = 0.022; 12 months, P < 0.001; double-segment PCS: preoperative, p = 0.890; 1 month, P = 0.374; 6 months, P = 0.022; 12 months, P = 0.023; MCS: preoperative, P = 0.447; 1 month, P = 0.419; 6 months, P = 0.023; 12 months, P < 0.001). At the final follow-up, there were no significant differences observed in fusion rates between the groups according to the Bridwell fusion grading system (P > 0.05), with both groups achieving satisfactory fusion rates. The modified MacNab criteria revealed that excellent and good results in each group were > 90%, with no significant differences being observed between the groups (P > 0.05). CONCLUSIONS: For the treatment of LDD in elderly patients, both TLIF combined with UPSF and TLIF combined with BPSF can achieve favourable outcomes. However, UPSF demonstrates advantages compared with BPSF, including a shorter surgery time, reduced intraoperative blood loss, and greater postoperative quality of life.