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Study Design. Analysis of the National Hospital Discharge Survey database from 1990 to 2007. Objective. To evaluate the influence of preoperative depression, anxiety, schizophrenia, or dementia on in-hospital (1) adverse events, (2) mortality, and (3) nonroutine discharge in patients undergoing major spine surgery. Summary of Background Data. Psychiatric comorbidity is a known risk factor for impaired health-related quality of life and poor long-term outcomes after spine surgery, yet little is known about its impact in the perioperative spine surgery setting. Methods. Using the National Hospital Discharge Survey database, all patients undergoing either spinal fusion or laminectomy between 1990 and 2007 were identified and separated into groups with and without psychiatric disorders. Multivariable regression analysis was performed for each of the outcome variables. Results. Between 1990 and 2007, a total estimated number of 5,382,343 spinal fusions and laminectomies were performed. The prevalence of diagnosed depression, anxiety, and schizophrenia among the study population increased significantly over time. Depression, anxiety, schizophrenia, and dementia were associated with higher rates of nonroutine discharge. Depression, schizophrenia, and dementia were associated with higher rates of adverse events. Dementia was the only psychiatric disorder associated with a higher risk of in-hospital mortality. Conclusion. Patients with preoperative psychiatric disorders undergoing major spine surgery are at increased risk for perioperative adverse events and posthospitalization care, but its effect in perioperative mortality is more limited. Presurgical psychological screening of candidates undergoing spine surgery might ultimately lead to the enhancement of perioperative outcomes in this growing segment of the US population. Conclusion. Level of Evidence: N/A