Pedicle screw loosening is a common postoperative complication for osteoporotic patients, and several studies have identified the important role of fusion length in internal fixation failure, but the relationship between the number of fusion segments and the potential risks remains unclear. This study aimed to investigate the rate and risk factors of screw loosening in osteoporotic patients with different levels of degenerative lumbar disease. The total cohort of 217 patients was divided into 3 groups according to the different fusion levels: single-level (group A; 100 cases), double-level (group B; 73 cases), and multilevel group (group C; 44 cases). Patient baseline demographic characteristics and assessments with a visual analog scale (VAS) and the Oswestry Disability Index (ODI) before operation and at the last follow-up were compared among the 3 groups. Compared with preoperative values, VAS and ODI scores at the last follow-up were significantly improved in all 3 groups. Operative time, blood loss, length of hospital stay, screw loosening rate, fusion rate, and VAS and ODI scores at the last follow-up obviously increased with the increasing number of fusion segments (group C> group B> group A). Of note, all the screw loosening was observed in cranial and caudal vertebra. Furthermore, multivariate logistic regression analysis identified lumbosacral fixation, larger pelvic incidence (PI)-lumbar lordosis (LL) difference (PT-LL), and greater postoperative pelvic tilt (PT) as independent predictors of screw loosening. However, sex, bone mineral density, body mass index, LL, sacral slope, PI, the change in LL, and preoperative PT were not relevant to screw loosening (P > 0.05). Owing to the high rate of screw loosening in cranial and caudal vertebra, osteoporotic patients with double-level or multilevel pedicle screw fixation benefited less than those with single-level pedicle screw fixation. Larger PI-LL, larger PT, and lumbosacral fixation are other risk factors for screw loosening. An instrument with stronger holding strength at cranial and caudal pedicle screws is recommended for those high-risk patients. Copyright © 2020 Elsevier Inc. All rights reserved.