Study Design. Retrospective review of the Healthcare Cost and Utilization Project National Inpatient Sample, 2000 to 2013. Objective. To determine the proportion of spinal epidural abscess (SEA) cases that were related to injection drug use (IDU) and to compare length of stay, leaving against medical advice, paralysis, cauda equina syndrome, radiculitis, and in-hospital mortality between SEA cases with and without IDU. Summary of Background Data. The US opioid epidemic impacts all aspects of healthcare, including spinal surgeons. Although injection drug use (IDU) is a risk factor for spinal epidural abscess (SEA), IDU among SEA patients and its effect on clinical outcomes is not well understood. Methods. Cases aged 15 to 64 with principal diagnosis of SEA were classified as IDU-related (IDU-SEA) or non-IDU-related (non-IDU-SEA) using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for illicit drug use and hepatitis C. We determined the proportion of SEA patients with IDU and compared length of stay, leaving against medical advice, paralysis, cauda equina syndrome, radiculitis, and in-hospital mortality between IDU-SEA and non-IDU-SEA patients. Results. From 2000 to 2013, there were 20,425 admissions with a principal diagnosis of SEA (95% confidence interval (CI), 19,281-21,568); 19.1% were associated with IDU (95% CI, 17.7%-20.5%). The proportion of white IDU-SEA cases increased by 2.4 percentage points annually (95% CI, 1.4-3.4). After adjusting for age, sex, and race, IDU-SEA patients stayed a mean of 6.7 more days in the hospital (95% CI, 5.1-8.2) and were 4.8 times more likely to leave against medical advice (95% CI, 2.9-8.0). Mean hospital charges for IDU-SEA patients were $31,603 higher (95% CI: $20,721-$42,485). Patients with IDU-SEA were less likely to have cauda equina syndrome (adjusted odds ratio, 0.48, 95% CI, 0.26-0.87). Conclusion. IDU-SEA patients stay in the hospital longer and more often leave against medical advice. Providers and hospitals may benefit from exploring how to better facilitate completion of inpatient treatment and achieve superior outcomes.