In this article, we report on our use of a 2-stage exchange in managing infected total hip arthroplasties (THAs) at the Hospital for Special Surgery in New York City. This protocol involves resection arthroplasty, 6 weeks of intravenous antibiotics to obtain a minimum "postpeak" serum bactericidal titer (SBT) of 1:8, and reimplantation. Over the past 20 years, we have conducted several studies showing the effectiveness of this treatment. Since our previous report was published in 1994, prevalence of multidrug-resistant (MDR) organisms has increased significantly. In 2008, we set out to determine if 2-stage exchange remains an effective treatment for newer pathogens, many of which are MDR. The overall eradication rate was 95% (80/84 hips). All 21 MDR pathogens implicated in the infected THAs were eradicated. We conclude that 2-stage exchange with a standard 1:8 minimum SBT remains an effective treatment even when resistant infections are involved.