STUDY DESIGN: A retrospective analysis of population-based national hospital discharge data collected for the Nationwide Inpatient Sample. OBJECTIVE: To examine the trends and in-hospital outcomes of patients with human immunodeficiency virus (HIV) infection undergoing spinal fusion on a national level. SUMMARY OF BACKGROUND DATA: Highly active antiretroviral therapy has provided healthier lives and prolonged the life expectancy of HIV-positive patients. However, few previous studies have reported trends and outcomes of HIV-positive patients undergoing spinal surgery. METHODS: Clinical data were derived from the US Nationwide Inpatient Sample between 2000 and 2009. Patients who underwent spinal fusion were identified. Data regarding HIV, patient- and health care system-related characteristics, comorbidities, in-hospital complications, and mortality were retrieved and analyzed. In-hospital outcomes were compared between HIV-positive and -negative patients and analyzed with the use of multivariate logistic regression. RESULTS: A total of 5,070 HIV-positive patients underwent spinal fusion in the United States during the last decade. From 2000 to 2009, population-adjusted incidence of HIV-positive patients who underwent spinal fusion has increased more than 3-fold (0.094 per 100,000 in 2000 to 0.303 per 100,000 in 2009; P < 0.001). Comparison between HIV-positive and -negative patients showed that HIV-positive patients had a significantly higher respiratory complication rate (6.2% vs. 3.2%), wound-related complication rate (2.7% vs. 1.7%), overall in-hospital complication rate (12.2% vs. 9.5%), and in-hospital mortality rate (1.6% vs. 0.3%), as well as longer hospital stay (6.6 d vs. 4.2 d). The risk of in-hospital mortality was 3.53 times higher in HIV-positive patients after controlling for other factors (95% confidence interval, 2.02-6.14; P < 0.001). CONCLUSION: During the last decade, the incidence of HIV-positive patients undergoing spinal fusion has increased in the United States. In this study, HIV infection was an independent risk factor for in-hospital mortality in patients undergoing spinal fusion. LEVEL OF EVIDENCE: 3.