Hip arthroplasty is a common surgical procedure, but the diagnosis of infection associated with hip arthroplasty remains challenging. Fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been shown to be a promising imaging modality in settings where infection is suspected. However, inflammatory reaction to surgery can result in increased FDG uptake at various anatomic locations, which may erroneously be interpreted as sites of infection. The purpose of this study was to assess the patterns and time course of FDG accumulation following total hip replacement over an extended period of time. Firstly, in a prospective study nine patients with total hip replacement were investigated to determine the patterns of FDG uptake over time. Three FDG-PET scans were performed in each patient at about 3, 6 and 12 months post arthroplasty. Secondly, in a retrospective analysis, the medical and surgical history and FDG-PET imaging results of 710 patients who had undergone whole-body scans for the evaluation of possible malignant disorders were reviewed. The history of arthroplasty and FDG-PET findings in the hip region were reviewed for this study. Patients with symptomatic arthroplasties or related complaints during FDG-PET scanning were excluded from the analysis. During the entire study period, all nine patients enrolled in the prospective study were demonstrated to have increased FDG uptake around the femoral head or neck portion of the prosthesis that extended to the soft tissues surrounding the femur. Among the patients reviewed in the retrospective study, 18 patients with a history of 21 hip arthroplasties who were asymptomatic at the time of FDG-PET scan met the criteria for inclusion. The time interval between the hip arthroplasty and the FDG-PET study ranged from 3 months to 288 months (mean+/-SD: 80.4+/-86.2 months). In 81% (17 of 21) of these prostheses, increased FDG uptake could be noted around the femoral head or neck portion of the prosthesis. The average time interval between arthroplasty and FDG-PET scan in these patients was 71.3 months. In only four prostheses (19%, 4 of 21) was no abnormally increased FDG uptake seen around the prostheses or adjacent sites. The average time interval in these patients was 114.8 months. It is concluded that following hip arthroplasty, non-specifically increased FDG uptake around the head or neck of the prosthesis persists for many years, even in patients without any complications. Therefore, to minimize the number of false-positive results for infection with PET studies obtained to evaluate a painful hip prosthesis, caution should be exercised when interpreting FDG uptake around the head or neck portion of the prosthesis.