BACKGROUND: Limitations in the operative microscope (OM)'s mobility and suboptimal ergonomics created the opportunity for the development of the exoscope. This systematic review aims to evaluate the advantages and disadvantages of exoscopes and OMs in spine surgery. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search was conducted in the major research databases. All studies evaluating the exoscopes and/or OMs in spinal procedures were included. RESULTS: There were 602 patients included in the 16 studies, with 539 spine surgery patients, 19 vascular cases, 1 neural pathology case, 19 cranial cases, and 24 tumor pathologies. When examining surgical outcomes with the exoscope, results were mixed. Compared to the OM, exoscope usage resulted in longer operative times in 7 studies, comparable times in 3 studies, and shorter operative times in 3 studies. Two studies found similar lengths of stay (LOS) for both tools, two reported longer LOS with exoscopes, and one indicated shorter hospital LOS with exoscopes. One study reported higher exoscope-related blood loss (EBL), but four other studies consistently showed reduced EBL. In terms of image quality, illumination, dynamic range, depth perception, ergonomics and cost-effectiveness, the exoscope was consistently rated superior, while findings across studies were mixed regarding the optical zoom ratio and mean scope adjustment (MSA). The learning curve for exoscope use was consistently reported as shorter in all studies. CONCLUSION: Exoscopes present a viable alternative to OMs in spine surgery, offering multiple advantages, which supports their promising role in modern neurosurgical practice.