We designed this retrospective study with aims to investigate the incidence and risk factors associated with surgical site infection (SSI) following posterior lumbar interbody fusion (PLIF) and instrumentation in patients with lumbar degenerative disease. Eligible patients treated between January 2016 and June 2019 were included. Electronic medical records were inquired for data extraction and collection. Patients with SSI and without SSI were compared using the univariate analyses, and the association between variables and risk of SSI was investigated using multivariate logistics regression analyses. Among 1269 patients, 43 were found to have SSI, indicating a rate of 3.4%. Microbiological culture tests showed 88.4% patients had a positive result. Four SSIs were caused by mixed bacterial, and the remaining 34 by single bacteria. Multiple drug-resistant strains were detected in 25 (65.8%) SSIs, with meticillin-resistant coagulase-negative staphylococcus (MRCNS) predominating (12, 48.0%). ASA III and above (odd ratio (OR), 1.67; 95% confidence interval (CI), 1.11 to 3.07), preoperative stay (OR, 1.13; 95% CI, 1.04 to 1.23), heart disease (OR, 2.88; 95% CI, 1.24 to 6.71), diabetes mellitus (OR, 3.28; 95% CI, 1.66 to 6.47) and renal insufficiency (OR, 4.23; 95% CI, 1.26 to 10.21), prolonged prophylactic antibiotics use (OR, 4.43; 95% CI, 2.30 to 8.54), and the reduced lymphocyte count (OR, 2.11; 95% CI, 1.03 to 4.33) were identified as independent risk factors associated with SSI. These factors, although most not modifiable, should be kept in mind, optimised for surgical conditions, or readily adjusted in the future postoperative management of antibiotics, to reduce postoperative SSIs.