Background In the acute postoperative period, fluid collections are common in lower extremity amputations. Whether these fluid collections increase the risk of infection is unknown. Questions/purposes The purposes of this study were to determine (1) the percentage of patients who develop postoperative fluid collections in posttraumatic amputations and the natural course of the collection; (2) whether patients who develop these collections are at increased risk for infection; and to ask (3) are there objective clinical or radiologic signs that are associated with likelihood of infection when a fluid collection is present?Methods We performed a review of all 300 patients injured in combat operations who sustained at least one major lower extremity amputation (at or proximal to the tibiotalar joint) and were treated definitively at our institution between March 2005 and April 2009. We segregated the groups based on whether cross-sectional imaging was performed less than 3 months (early group) after closure, greater than 3 months (late group) after closure, or not at all (control group, baseline frequency of infection). Our primary study cohort where those patients with a fluid collection in the first three months. The clinical course was reviewed and the primary outcome was a return to the operating room for irrigation and débridement with positive cultures. For those patients with cross-sectional imaging, we also collected objective clinical parameters within 24 hours of the scan (white blood cell count, maximum temperature, presence of bacteremia, tachycardia, oxygen desaturation), extremity examination (presence of erythema, warmth, and/or drainage), and characteristics of the fluid collections seen (size of the fluid collection, Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.