This study aimed to identify risk factors for deep surgical site infection (SSI) following open posterior lumbar fusion (OPLF). We retrospectively analyzed the clinical data of patients who underwent OPLF between January 2014 and December 2022. Patients were divided into SSI and non-SSI groups according to whether deep SSI occurred following OPLF. Patient’s sex, age, body mass index (BMI), history of diabetes mellitus and smoking, American Society of Anesthesiologists score, surgical segment, surgical time, preoperative albumin level, local use of vancomycin, and cerebrospinal fluid (CSF) leakage were compared between the 2 groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for postoperative deep SSI. The deep SSI rate was 5.0% (63/1256). Among them, age (P < .001), BMI (P = .008), surgical segment (P < .001), surgical time (P < .001), prevalence of diabetes mellitus (P = .036), and CSF leakage (P < .001) were significantly higher in the SSI group, whereas the preoperative albumin level (P < .001) and proportion of local use of vancomycin (P = .046) were significantly lower in the SSI group than those in the non-SSI group. Multivariate analysis indicated that higher age (P = .046, odds ratio [OR]: 1.036, 95% confidence interval [CI]: 1.001–1.073), BMI (P = .038, OR: 1.113, 95% CI: 1.006–1.232), lower preoperative albumin level (P = .041, OR: 0.880, 95% CI: 0.778–0.995), higher surgical segment (P = .004, OR: 2.241, 95% CI: 1.297n3.871), and CSF leakage (P = .046, OR: 2.372, 95% CI: 1.015–5.545) were risk factors, and the local use of vancomycin (P < .001, OR: 0.093, 95% CI: 0.036–0.245) was the protective factor for deep SSI following OPLF. We identified 5 risk factors (older age and BMI, lower preoperative albumin level, higher surgical segment, and CSF leakage) and 1 protective factor (local use of vancomycin powder) for deep SSI following OPLF. To address these risk and protective factors, comprehensive evaluations and recommendations should be provided to patients to reduce SSI rates.