OBJECT This study evaluated the efficacy and safety of mini-open anterior debridement and lumbar interbody fusion in combination with posterior percutaneous fixation for single-level lumbar pyogenic spondylodiscitis. METHODS This is a retrospective study. Twenty-two patients with single-level lumbar pyogenic spondylodiscitis underwent mini-open anterior debridement and lumbar interbody fusion in combination with posterior percutaneous fixation via a modified anterior lumbar interbody fusion (ALIF) approach. Patients underwent follow-up for 24 to 38 months. Clinical data, etiological examinations, operative time, intraoperative blood loss, American Spinal Injury Association (ASIA) grade, Japanese Orthopaedic Association (JOA) lumbar function score, visual analog scale (VAS) score, Oswestry Disability Index (0D1), postoperative complications, and the bony fusion rate were recorded. RESULTS The mean operative time was 181.1 +/- 22.6 minutes (range 155-240 minutes). The mean intraoperative blood loss was 173.2 +/- 70.1 ml (range 100-400 ml). Infection was found in lumbar vertebrae L2-3, L3-4, and L4-5 in 2, 6, and 14 patients, respectively. Bacterial cultures were positive in 15 patients, including 4 with Staphylococcus aureus, 6 with Staphylococcus epidermidis, 4 with Streptococcus, and 1 with Escherichia coli. Postoperative complications included urinary retention, constipation, and numbness in the thigh in 5, 3, and 2 patients, respectively. Compared with before surgery, the VAS scores and 0131 were significantly lower at the final follow-up, the JOA scores were significantly higher, and the ASIA grades had improved. All patients achieved good intervertebral bony fusion. CONCLUSIONS Mini-open anterior debridement and lumbar interbody fusion in combination with posterior percutaneous fixation via a modified ALIF approach results in little surgical trauma and intraoperative blood loss, acceptable postoperative complications, and is effective and safe for the treatment of single-level lumbar pyogenic spondylodiscitis. This approach could be an alternative to the conventional open surgery.