OBJECTIVE Depression is the most prevalent affective disorder in the US, and patients with spinal deformity are at increased risk. Postoperative delirium has been associated with inferior surgical outcomes, including morbidity and mortality. The relationship between depression and postoperative delirium in patients undergoing spine surgery is relatively unknown. The aim of this study was to determine if depression is an independent risk factor for the development of postoperative delirium in patients undergoing decompression and fusion for deformity. METHODS The medical records of 923 adult patients (age ? 18 years) undergoing elective spine surgery at a single major academic institution from 2005 through 2015 were reviewed. Of these patients, 255 (27.6%) patients had been diagnosed with depression by a board-certified psychiatrist and constituted the Depression group; the remaining 668 patients constituted the No-Depression group. Patient demographics, comorbidities, and intra- and postoperative complication rates were collected for each patient and compared between groups. The primary outcome investigated in this study was rate of postoperative delirium, according to DSM-V criteria, during initial hospital stay after surgery. The association between depression and postoperative delirium rate was assessed via multivariate logistic regression analysis. RESULTS Patient demographics and comorbidities other than depression were similar in the 2 groups. In the Depression group, 85.1% of the patients were taking an antidepressant prior to surgery. There were no significant between-group differences in intraoperative variables and rates of complications other than delirium. Postoperative complication rates were also similar between the cohorts, including rates of urinary tract infection, fever, deep and superficial surgical site infection, pulmonary embolism, deep vein thrombosis, urinary retention, and proportion of patients transferred to the intensive care unit. In total, 66 patients (7.15%) had an episode of postoperative delirium, with depressed patients experiencing approximately a 2-fold higher rate of delirium (10.59% vs 5.84%). In a multivariate logistic regression analysis, depression was an independent predictor of postoperative delirium after spine surgery in spinal deformity patients (p = 0.01). CONCLUSIONS The results of this study suggest that depression is an independent risk factor for postoperative delirium after elective spine surgery. Further studies are necessary to understand the effects of affective disorders on postoperative delirium, in hopes to better identify patients at risk.