Retrospective observational cohort study.We used observational measures and retrospective chart reviews to compare elderly patients with osteoporosis who underwent multi-level anterior lumbar interbody fusion (ALIF) with either posterolateral fusion (PLF) or percutaneous pedicle screw fixation.Multi-level ALIF with PLF is used to save the posterior element of the spine and improve fusion rates in elderly patients with osteoporosis. To minimize perioperative invasiveness and improve patients’ postoperative quality of life, we perform minimal percutaneous screw fixation.Fifty-three elderly patients with osteoporosis who underwent either PLF with open pedicle screw fixation (n = 28) or percutaneous pedicle screw fixation (PPF) (n = 25) for treatment with 2-level ALIF between January 2010 and December 2013 were compared for clinical outcome including operation time, intraoperative and postoperative blood loss, and hospital day and radiological outcome.Average operation times were significantly shorter and intra- and postoperative blood loss was significantly reduced in the PPF group. There were no significant differences, preoperative and postoperative, in observational measures including visual analog scale, Oswestry disability index, and Rolland-Moris disability. There were no significant differences in the degree of lordosis, changes of motion, or adjacent segmental degeneration. Fusion rates were increased in the PLF group compared to the PPF group 6 months post-surgery, but from 1 year to the last follow-up, the rates were statistically equivalent. There were fewer minor complications in the PPF group, and no major complications at all.Two-level ALIF with PPF results in shorter operation times, less blood loss and minor complications, and similar fusion rate as 2-level ALIF with PLF. It; therefore, represents an effective method, leading to rapid recovery and less complications in elderly patients with osteoporosis.