Aims. A variety of surgical methods and strategies have been demonstrated for Andersson lesion (AL) therapy. In 2011, we proposed and identified the feasibility of stabilizing the spine without curettaging the vertebral or discovertebral lesion to cure non-kyphotic AL. Additionally, due to the excellent reunion ability of ankylosing spondylitis, we further came up with minimally invasive spinal surgery (MIS) to avoid the need for both bone graft and lesion curettage in AL surgery. However, there is a paucity of research into the comparison between open spinal fusion (OSF) and early MIS in the treatment of AL. The purpose of this study was to investigate and compare the clinical outcomes and radiological evaluation of our early MIS approach and OSF for AL. Methods. A total of 39 patients diagnosed with AL who underwent surgery from January 2004 to December 2022 were retrospectively screened for eligibility. Patients with AL were divided into an MIS group and an OSF group. The primary outcomes were union of the lesion on radiograph and CT, as well as the visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores immediately after surgery, and at the follow-up (mean 29 months (standard error (SE) 9)). The secondary outcomes were total blood loss during surgery, operating time, and improvement in the radiological parameters: global and local kyphosis, sagittal vertical axis, sagittal alignment, and chin-brow vertical angle immediately after surgery and at the follow-up. Results. Data for 30 patients with AL were evaluated: 14 in the MIS group and 16 in the OSF group. All patients were followed up after surgery; no nonunion complications or instrumentation failures were observed in either group. No significant differences in the VAS and ODI scores were identified between the two groups. Mean ODI improved from 51 (SE 5) to 17 (SE 5) in the MIS group and from 52 (SE 6) to 19 (SE 5) in the OSF group at the follow-up. There were significant improvements in total blood loss (p = 0.025) and operating time (p < 0.001) between the groups. There was also no significant difference in local kyphosis six months postoperatively (p = 0.119). Conclusion. Early MIS is an effective treatment for AL. MIS provides comparable clinical outcomes to those treated with OSF, with less total blood loss and shorter operating time. Our results support and identify the feasibility of solid immobilization achieved by posterior instrumentation without bone graft via MIS for the treatment of AL. Cite this article: Bone Jt Open 2024;5(10):886–893