Background: The effect and potential risks of CAPSI on osteoporotic lumbar degenerative disease (LDD) have not been investigated in the cases of multilevel fixation. This study was to investigate potential complications of using multilevel cement-augmented pedicle screws fixation (three or four levels) and its effectiveness of this method on treating LDD with low bone quality. Methods: A total of 93 patients with multilevel LDD were divided into the CAPSI group (46 subjects) and the CPS group (47 subjects), including 75 cases for three levels, 18 cases for four levels, and the average follow-up was 33.72±18.78 months (range: 24-108). Relevant data were recorded, including age, gender, body mass index (BMI), bone mineral density (BMD), diagnosis, fusion methods, bone graft, fusion level, lumbosacral fixation, different patterns of S1 pedicle screw placement, operation time, blood loss, hospital stay, perioperative complications, CL, pulmonary cement embolism (PCE), screw loosening, and nonunion patients. Furthermore, we also measured the VAS and ODI at pre-operation, post-operation, and follow-up time points. Results: In the CAPSI group, a total of 336 augmented screws was placed bilaterally, and the average injection dose of bone cement was 1.85±0.65 ml (range: 1-4). The CL was observed in 44 patients (95.65%) and 116 screws (34.52%). And in the CPS group, seventeen patients (36.17%) and thirty-three screws (8.46%) suffered loosening in cranial or caudal vertebra (seven cranial cases and twenty-six of caudal), four cases experienced nonunion, and thus the fusion rate was 91.49% in total. The operation time and hospital stay of CAPSI group were longer than the CPS group, but CAPSI group has a lower screw loosening percentage ( P <0. 05). And in terms of blood loss, perioperative complications, fusion rate, VAS and ODI scores at the follow-up times, there were no significant differences between two groups. Conclusions: Patients with osteoporotic LDD underwent multilevel CPS fixation have a higher rate of screw loosening in cranial and caudal vertebra. The application of cemented pedicle screws for multilevel LDD can achieve better stability and less screw loosening, but it also accompanied by longer operating time, higher incidence of CL, PCE and wound infections.