BACKGROUND:: Perioperative visual loss, a rare but dreaded complication of spinal fusion surgery, is most commonly caused by ischemic optic neuropathy (ION). The authors sought to determine risk factors for ION in this setting. METHODS:: Using a multicenter case-control design, the authors compared 80 adult patients with ION from the American Society of Anesthesiologists Postoperative Visual Loss Registry with 315 adult control subjects without ION after spinal fusion surgery, randomly selected from 17 institutions, and matched by year of surgery. Preexisting medical conditions and perioperative factors were compared between patients and control subjects using stepwise multivariate analysis to assess factors that might predict ION. RESULTS:: After multivariate analysis, risk factors for ION after spinal fusion surgery included male sex (odds ratio [OR] 2.53, 95% CI 1.35-4.91, P = 0.005), obesity (OR 2.83, 95% CI 1.52-5.39, P = 0.001), Wilson frame use (OR 4.30, 95% CI 2.13-8.75, P < 0.001), anesthesia duration (OR per 1 h = 1.39, 95% CI 1.22-1.58, P < 0.001), estimated blood loss (OR per 1 l = 1.34, 95% CI 1.13-1.61, P = 0.001), and colloid as percent of nonblood replacement (OR per 5% = 0.67, 95% CI 0.52-0.82, P < 0.001). After cross-validation, area under the curve = 0.85, sensitivity = 0.79, and specificity = 0.82. CONCLUSIONS:: This is the first study to assess ION risk factors in a large, multicenter case-control fashion with detailed perioperative data. Obesity, male sex, Wilson frame use, longer anesthetic duration, greater estimated blood loss, and decreased percent colloid administration were significantly and independently associated with ION after spinal fusion surgery.