Previous studies to identify risk factors for postoperative deep infection following instrumented spinal fusion surgery for degenerative spinal disease are based on insufficient information and have limited use in clinical practice. This study aims to fill this gap by assessing the risk factors and their adjusted relative risks through a comprehensive analysis, including all core information. In this nationwide, population-based, cohort study, data were obtained from the Korean National Health Insurance claims database between 1 January 2014, and 31 December 2018. This study included a cohort of 194,036 patients older than 19 years, who underwent instrumented spinal fusion surgery for degenerative spinal disease. We divided this population into cases (patients with postoperative deep infection) and controls (patients without postoperative deep infection); risk factors for postoperative deep infection were determined by multivariable analysis. The definition of postoperative deep infection varied, and sensitivity analyses were performed according to each definition. The estimates of all the statistical models were internally validated using bootstrap samples. The study included 767 patients (0.39%) with postoperative deep spinal infections and 193,269 controls. The final multivariable model identified the following variables as significant risk factors for postoperative deep infection: age between 60–69 years (OR = 1.6 [1.1–2.3]); age between 70–79 years (OR = 1.7 [1.2–2.5]); age > 80 years (OR = 2.1 [1.3–3.2]); male sex (OR = 1.7 [1.5–2.0]); rural residence (OR = 1.3 [1.1–1.5]); anterior cervical approach (OR = 0.2 [0.1–0.3]); posterior cervical approach (OR = 0.5 [0.2–1.0]); multiple approaches (OR = 1.4 [1.2–1.6]); cerebrovascular disease (OR = 1.5 [1.2–1.8]); peripheral vascular disease (OR = 1.3 [1.1–1.5]); chronic pulmonary disease (OR = 1.2 [1.0–1.4]); rheumatologic disease (OR = 1.6 [1.3–2.1]); liver disease (OR = 1.4 [1.1–1.7]); diabetes (OR = 1.5 [1.3–1.7]); hemiplegia or paraplegia (OR = 2.2 [1.5–3.3]); allogenous transfusion (OR = 1.6 [1.3–1.8]); and use of systemic steroids over 2 weeks (OR = 1.5 [1.1–2.0]). Our results, which are based on homogenous patient groups, provide clinicians with an acceptable tool for comprehensive risk assessment of postoperative deep infection in patients who will undergo instrumented spinal fusion surgery for degenerative spinal disease.