Objective To examine the relative incidence of newly recorded diagnosis of depression after spinal surgery as a proxy for the risk of post–spinal surgery depression. Patients and Methods We used the longitudinal California Office of Statewide Health Planning and Development database (January 1, 2000, through December 31, 2010) to identify patients who underwent spinal surgery during these years. Patients with documented depression before surgery were excluded. Risk of new postoperative depression was determined via the incidence of newly recorded depression on any hospitalization subsequent to surgery. For comparison, this risk was also determined for patients hospitalized during the same time period for coronary artery bypass grafting, hysterectomy, cholecystectomy, chronic obstructive pulmonary disease, congestive heart failure exacerbation, or uncomplicated vaginal delivery. Results Our review identified 1,078,639 patients. Relative to the uncomplicated vaginal delivery cohort, the adjusted hazard ratios (HRs) for newly recorded depression within 5 years after the admission of interest were 5.05 for spinal surgery (95% CI, 4.79-5.33), 2.33 for coronary artery bypass grafting (95% CI, 2.15-2.54), 3.04 for hysterectomy (95% CI, 2.88-3.21), 2.51 for cholecystectomy (95% CI, 2.35-2.69), 2.44 for congestive heart failure exacerbation (95% CI, 2.28-2.61), and 3.04 for chronic obstructive pulmonary disease (95% CI, 2.83-3.26). Among patients who underwent spinal surgery, this risk of postoperative depression was highest for patients who underwent fusion surgery (HR, 1.28; 95% CI, 1.22-1.36) or had undergone multiple spinal operations (HR, 1.22; 95% CI, 1.16-1.29) during the analyzed period. Conclusion Patients who undergo spinal surgery have a higher risk for postoperative depression than patients treated for other surgical or medical conditions known to be associated with depression.