Background: Acute postoperative infection after total hip arthroplasty (THA) is typically treated with irrigation and débridement and exchange of the modular femoral head and acetabular liner. Given a rate of failure exceeding 50% in some series, a one-stage exchange has been suggested as a potential alternative because it allows more thorough débridement and removal of colonized implants. To date, most studies published on the one-stage exchange have used microbe-specific antibiotic-laden bone cement with only one small single-institution series that reported outcomes after a cementless one-stage exchange. Questions/purposes: We determined whether a one-stage cementless exchange for treating acute postoperative infection after THA would result in infection control with component retention and normalization of infection markers. Methods: We retrospectively identified 27 patients who underwent a one-stage exchange performed for an acute (≤ 6 weeks) postoperative infection after THA from April 2004 to December 2009. Primary cementless components were used both at the time of the index arthroplasty and the revision in all patients. Surgery was followed by a 6-week course of culture-specific antibiotics in all patients and a variable course of oral antibiotics. Our primary outcome was retention of the implants at most recent followup and our secondary outcome was normalization of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at most recent followup. Patients were followed until failure or a minimum of 2 years. Results: At a minimum followup of 27 months (mean, 50 months; range, 27-89 months), 19 of the 27 patients (70%) retained their implants but four required further operative débridement with component retention at a mean of 3 weeks (range, 2-6 weeks) to obtain control of infection. Thus, an isolated single-stage exchange was successful in 15 of the 27 patients (56%). Eight patients (30%) ultimately had a two-stage exchange for persistent infection; seven of these patients required no further surgery, whereas one patient required a second two-stage exchange. Of those patients retaining their prosthesis after one-stage exchange and tracked with ESR and CRP, four (33% [four of 12]) had elevated values without other signs or symptoms of recurrent infection. Conclusions: For acute postoperative infection after primary THA, a one-stage cementless exchange allowed 70% of patients to retain their implants at most recent followup. Of those patients who ultimately went on to a two-stage exchange, only one required a second two-stage exchange. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.