Background: The association between wound drainage and subsequent periprosthetic infection is well known. However, the most appropriate treatment of wound drainage is not well understood. Methods: We retrospectively reviewed the records of 10325 patients (11785 procedures), among whom 300 patients (2.9%) developed persistent (greater than 48 hours postoperatively) wound drainage. Wound drainage stopped spontaneously between 2 and 4 days in 217 patients treated with local wound care and oral antibiotics. The remaining 83 patients (28%) underwent further surgery.Results: A single débridement resulted in cessation of drainage without subsequent infection in 63 of 83 patients (76%), whereas 20 (24%) patients continued to drain and underwent additional treatment (repeat débridement, resection arthroplasty, or long-term antibiotics). Timing of surgery and the presence of malnutrition predicted failure of the first débridement. There were no differences between the success and failure groups with regard to all other examined parameters, including demographic or surgical factors.Conclusions: We found patients who underwent débridement at a mean of 5 days following the onset of drainage were more likely to be infection free at one year postoperatively compared to patients who underwent debridement at a delayed time (mean, 10 days). Our data confirmed that malnourished patients (serum transferrin less than 200 mg/dL, serum albumin less than 3.5 g/dL, or total than 1500/mm3) undergoing total joint arthroplasty are lymphocyte count less more likely to develop deep infection and require further treatment after irrigation and débridement. Based on these findings, we recommend early (within 7 days) surgery for persistent wound drainage in general, and particularly for those with malnutrition