Objective To evaluate the clinical efficacy and safety of debridement via unilateral intervertebral foraminal approach combined with single-segment fixation of the diseased spines in treating thoracolumbar intervertebral infection. Methods Clinical data of 116 patients who received treatment for thoracolumbar intervertebral infection from January 2013 to January 2022 were analyzed retrospectively. Patients were divided into two groups based on the surgical approach. Group A (n=49) underwent debridement via unilateral intervertebral foraminal approach combined with single-segment fixation of the diseased vertebra, while group B (n=67) underwent debridement via posterior total laminectomy and bone graft fusion combined with internal fixation. Clinical and imaging results of two groups of patients were compared. Results No significant differences were found between the two groups in sex, age, body mass index, affected segment, and pathogenic distribution (all P>0.05). Group A had shorter operative duration, less intraoperative blood loss, shorter postoperative hospital stay, and lower hospitalization costs than group B (all P<0.05). There was no statistically significant difference in intervertebral fusion time between the two groups of patients (P>0.05). Repeated-measures analysis of variance showed significant time effect for visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, and Oswestry disability index (ODI) (all P<0.001), indicating postoperative pain and functional status in both groups of patients improved markedly compared with preoperative status. The group effect and group × time interaction effect for these scores were not statistically significant (all P>0.05), suggesting the differences in overall efficacy and changing trend over time between the two groups were not significant. There was no statistically significant diffe-rence in American Spinal Injury Association (ASIA) grading and neurological function improvement between the two groups of patients (both P>0.05). Conclusion For patients with thoracolumbar intervertebral infection who meet the surgical indications, debridement via unilateral intervertebral foraminal approach combined with single-segment fixation of the diseased vertebra can achieve similar clinical efficacy and safety to debridement via posterior total laminectomy and bone graft fusion combined with internal fixation. At the same time, it has the advantages of shorter surgical duration, less intraoperative blood loss, shorter postoperative hospital stay, and lower hospitalization costs, and may serve as a less invasive posterior surgical approach.