Abstract：[Objective] To compare clinical efficacy between transforaminal lumbar interbody fusion(TLIF) combined with unilateral and bilateral cement-augmented pedicle screw technique applied on the patients in the osteoporotic spine with two-segment lumbar degenerative disease. [Methods] Fifty-nine patients with two-segment lumbar degenerative disease were enrolled in our institute with retrospectively reviewed from January 2016 to December 2018, which had been receiving TLIF combined with augmented pedicle trajectory technique. They were divided into two groups: 31 cases were in the unilateral pedicle trajectory augmented group and the other 28 cases were in the bilateral pedicle trajectory augmented group. Surgical data including operation time，intra-operative blood loss，hospitalization day and surgical complications were recorded, as well as the radiological parameters measured from postoperative images including the rates of fusion and screw loosening. In addition, the low back pain and leg pain were represented as Visual Analogue Scale (VAS) score. The preoperative and postoperative Oswestry Disability Index (ODI) score were recorded individually to evaluate patients' functional recovery. Besides, the MacNab criterion was used for assessment of postoperative efficacy. [Results] The operation was successfully completed in both groups. Compared with bilateral pedicle trajectory augmented group, operation time and cement leakage rate in unilateral pedicle trajectory augmented group decreased significantly (P＜0.05). While no statistical difference for the average hospital stay and blood loss was found between 2 groups(P>0.05). All the patients were followed up for 14~48 months, the average follow-up time was 24.63±9.22 months. There were no screw loosening, breakage and cage sliding in all patients. After surgeries, low back VAS, leg VAS and ODI at 3 months and final follow-up improved significantly in two groups(P<0.05). There were no significant differences of VAS and ODI preoperatively and postoperatively between 2 groups(P>0.05). In the unilateral pedicle trajectory augmented group, the fusion rate was 93.55%, the excellent and good rate was 94.8%. In the bilateral pedicle trajectory augmented group, the fusion rate was 96.43%, the excellent and good rate was 92.86%, however, no significant difference was found between 2 groups(P>0.05). Conclusion: TLIF combined with unilateral or bilateral cement augmented screw is safe and efficient for the treatment of patients in the osteoporotic spine with two-segment lumbar degenerative disease, but the unilateral augmented pedicle trajectory technique can significantly reduce the operation time and the incidence of cement leakage. It is worthy of further application in clinic work.