This retrospective cohort study aims to investigate the clinical outcomes of Girdlestone resection arthroplasty (GRA) in injection drug users with septic hip arthritis. Patients who underwent primary GRA for septic hip arthritis secondary to injection drug use at two academic trauma centers from 2015 to 2023 were retrospectively reviewed. Patient demographics, surgical details, and follow-up outcomes, including patient-reported outcome measures, were collected and analyzed. The cohort included 15 patients, with a mean age of 44 ± 11 years and a mean follow-up period of 25 ± 20 months. Among the 15 patients, overall mortality was 27%, and only 4 patients underwent total hip arthroplasty (THA) following GRA. Infection resolution rates were significantly higher in patients who received an antibiotic spacer (75% vs. 0%, p = 0.048). GRA in injection drug users is associated with high mortality and low conversion rates to THA. The use of an antibiotic spacer during GRA significantly improves infection resolution rates. Larger studies are required to determine the optimal management strategies for this patient population.