Background:Acute periprosthetic joint infection (PJI) is difficult to treat. In this study, we investigated the failure rates of irrigation and debridement (I&D) among patients with acute post-surgical and acute hematogenous PJI, and explored various host and organism-related risk factors that may be associated with treatment failure.Methods:We retrospectively reviewed the cases of 199 total joint arthroplasty patients who underwent I&D for acute post-surgical PJI (<3 months postoperatively) and acute hematogenous PJI (≥3 months postoperatively, with abrupt symptoms lasting <3 weeks) at a single center during the period of 2005 to 2016. Only patients meeting the Musculoskeletal Infection Society (MSIS) criteria for PJI were included. Patient demographics, comorbidities, physical examination findings, laboratory results, and organism profile were identified. Treatment failure, as defined by the Delphi criteria, was determined for 1-year follow-up. Primary statistical analysis involved univariate and multivariate regression.Results:The failure rate was 37.7% (75 of 199) at 1 year. Among the patients with acute hematogenous infections, the rate of failure (56%, 29 of 52) was almost 2 times higher than that of patients with acute post-surgical infections (31%, 46 of 147) (adjusted odds ratio [OR], 2.36; 95% confidence interval [CI], 1.16 to 4.81; p = 0.018). Host predictors of failure included prior revision surgery (adjusted OR, 2.55; 95% CI, 1.22 to 5.32; p = 0.013) and a higher Charlson Comorbidity Index (adjusted OR, 1.22; 95% CI, 1.01 to 1.51; p = 0.048). Specific comorbidities associated with failure included chronic obstructive pulmonary disease (p = 0.026), diabetes (p = 0.004), and a history of malignancy (p = 0.005). Patients with polymicrobial infections (adjusted OR, 2.40; 95% CI, 1.10 to 5.20; p = 0.028) were also more likely to experience failure of treatment after I&D. The clinical and laboratory risk factors associated with failure were the presence of intraoperative purulence (p = 0.05), elevated systolic blood pressure (p = 0.05), tachycardia (p = 0.06), and higher serum C-reactive protein level (p = 0.003).Conclusions:This study revealed that I&D is associated with a high rate of failure for patients with an acute hematogenous PJI. The study also identified a number of risk factors for failure. The findings of this study may allow better decision-making by surgeons regarding the surgical management of patients with acute PJI.Level of Evidence:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.