Abstract INTRODUCTION High-grade spondylolisthesis is a relatively uncommon condition. The optimal surgical approach for management remains debatable. Although in-situ fusion is preferred due to its lower risk of neural injury, it does not correct spinal alignment. In contrast, reduction corrects the deformity and provides a high rate of fusion, but has the potential for high rates of neural injury. We herein report our experience and surgical outcomes following minimally invasive versus open management of intermediate- to high-grade spondylolisthesis. METHODS A multicenter, retrospective cohort analysis of adult patients aged more than 18 yr with grade II or higher spondylolisthesis, who underwent surgery from January 2008 until February 2019, was performed. RESULTS Sixty-two patients were included in the final analysis. A total of 41 patients were treated with an open approach and 21 with a minimally invasive surgical approach (MIS). More specifically, 18 patients underwent in-situ fusion, 11 underwent MIS reduction, and 33 had an open reduction. The total rate of complications was 40.3%. The rate of complications in the MIS group was 52.3% compared to 34.1% in the open surgery group (P = .166). The rate of complications was 27.8% in the in-situ fusion group, 72.7% in the MIS-reduction group, and 36.4% in the open-reduction group. Our comparisons of the rate of complications in the no-reduction group vs the MIS-reduction group, and the MIS-reduction group vs the open-reduction group were statistically significant (P = .027 and P = .07, respectively). However, there was no statistically significant difference between the rate of complications in the no-reduction group vs the open-reduction group (P = .757), nor between the rate of complications in the MIS group vs the open surgery group (P = .166). CONCLUSION MIS reduction is associated with a high rate of complications in the management of high-grade spondylolisthesis.