Background/Objectives: The access route to the surgical treatment of pyogenic spondylitis is a critical issue. However, no published clear guidelines are available about the access route for the surgical treatment of pyogenic spondylitis. The objective of this study was to compare clinical outcomes according to surgical treatment approach (anterior approach with or without posterior approach versus posterior only approach) of pyogenic spondylitis. Methods: This study included patients who underwent surgical treatment for pyogenic spondylitis. These patients were divided into two groups according to surgical treatment approach: anterior approach with/without posterior approach (anterior group) and posterior-only approach (posterior group). Their baseline data, treatment failure, radiologic outcome, and ambulatory ability were compared. Results: Demographic data and clinical characteristics were similar (p > 0.05) between the two groups. Baseline radiologic characteristics of infection, including infected spinal level, number of infected segments, presence of epidural abscess, and vertebral body collapse, were also comparable between the two groups. The number of unplanned surgeries was less in the anterior group than in the posterior group (p < 0.05). Approach-related complications tended to occur more often in the anterior group, although the difference was not statistically significant (p = 0.067). There was no significant difference in radiologic outcome or final ambulation ability after surgery between the two groups (p > 0.05). Conclusions: Anterior approach with or without posterior approach offers fewer treatment failure rates, particularly regarding revision surgeries, than a posterior-only approach. Thus, an anterior approach with or without a posterior approach should be used when planning surgical treatment for pyogenic spondylitis.