Retrospective case series. We sought to identify risk factors associated with surgical site infection (SSI) after posterior long segment spinal fusion (PLSF). Patients who undergo PLSF may be at elevated risk of SSI. Identifying factors associated with SSI in these operations can help risk stratify patients and tailor management. We analyzed PLSFs-seven or more levels-at our institution from 2000 to 2015. Data on patients' clinical characteristics, procedural factors, and antimicrobial management were collected. Multivariable analysis identified factors independently associated with outcomes of interest. In 628 cases, SSI was associated with steroid use (P = 0.024, odds ratio [OR] = 2.54) and using cefazolin (P < 0.001, OR = 4.37) or bacitracin (P = 0.010, OR 3.49) irrigation, as opposed to gentamicin or other irrigation. Gram-positive infections were more likely with staged procedures (P = 0.021, OR 4.91) and bacitracin irrigation (P < 0.001, OR = 17.98), and less likely with vancomycin powder (P = 0.050, OR 0.20). Gram-negative infections were more likely with a history of peripheral arterial disease (P = 0.034, OR = 3.21) or cefazolin irrigation (P < 0.001, OR 25.47). Readmission was more likely after staged procedures (P = 0.003, OR = 3.31), cervical spine surgery (P = 0.023, OR = 2.28), or cefazolin irrigation (P = 0.039, OR = 1.85). Reoperation was more common with more comorbidities (P = 0.022, OR 1.09), staged procedures (P < 0.001, OR = 4.72), cervical surgeries (P = 0.013, OR = 2.36), more participants in the surgery (P = 0.011, OR = 1.06), using cefazolin (P < 0.001, OR = 3.12) or bacitracin (P = 0.009, OR = 3.15) irrigation, and higher erythrocyte sedimentation rate at readmission (P = 0.009, OR = 1.04). Washouts were more likely among patients with more comorbidities (P = 0.013, OR = 1.16), or who used steroids (P = 0.022, OR = 2.92), and less likely after cervical surgery (P = 0.028, OR = 0.24). Instrumentation removal was more common with bacitracin irrigation (p = 0.013, OR = 31.76). Patient factors, whether a procedure is staged, and choice of antibiotic irrigation affect the risk of SSI and ensuing management required.Level of Evidence: 4.