Introduction: The etiology of lumbar spine revision surgery is multifactorial, involving mechanical, biological, and clinical factors that challenge sustained spinal stability. Comparative analysis reveals significantly higher complication rates, prolonged hospital stays, and increased costs for revision surgeries compared to primary fusions despite low mortality rates. Leveraging a comprehensive dataset of 456,750 patients, this study identifies predictors of revision surgery and provides actionable insights to enhance patient outcomes and optimize healthcare resource allocation. Methods: A total of 456,750 patients registered in the National Inpatient Sample (NIS) database from 2016 to 2019 were identified as having undergone single-level lumbar fusion surgery (primary fusion: 99.5%; revision fusion: 0.5%). Multivariable logistic regression models adjusted for patient demographics, clinical comorbidities, and hospital characteristics were constructed to evaluate clinical outcomes and postoperative complications. Results: Patients undergoing revision lumbar fusion surgery were significantly younger compared to those experiencing primary fusion procedures (53.92 ± 20.65 vs. 61.87 ± 12.32 years, P < 0.001); among the entire cohort, 56.4% were women. Compared with patients undergoing primary lumbar fusion, those undergoing revision fusion surgery were significantly more likely to experience surgical site infections (odds ratio [OR] 27.10; 95% confidence interval [95% CI] 17.12–42.90; P < 0.001), urinary tract infections (OR 2.15; 95% CI 1.39–3.33; P < 0.001), and prolonged length of stay (OR 1.53; 95% CI 1.24–1.89; P < 0.001). Revision surgery patients had significantly lower odds of incurring high-end hospital charges (OR 0.65; 95% CI 0.51–0.83; P < 0.001). Other complications, including respiratory complications, dural tears, thromboembolic events, and acute renal failure, showed no statistically significant differences between the two groups. In-hospital mortality rates were low and did not differ significantly between groups (revision: 0.2% vs. primary: 0.1%, OR 3.29; 95% CI 0.45–23.84; P = 0.23). Conclusions: Patients undergoing revision lumbar fusion surgeries face significantly higher risks of surgical site infections, urinary tract infections, and prolonged hospital stays compared to primary fusion procedures. These findings highlight the need for targeted interventions to improve perioperative management and reduce complications in revision lumbar fusion surgery.