Successful treatment of prosthetic joint infections (PJIs) requires surgical intervention and prolonged antimicrobial therapy (AT), although the most suitable management has not been clearly defined yet. The aim of the study is to review our experience in the management of AHPJIs. From 01/01/2004 to 31/12/2006 all patients with PJIs were prospectively evaluated in 8 Spanish hospitals by the REIPI. We focused here on AHPJIs. Diagnostic of infection was based on clinical-microbiological evidence. Forty-nine patients, 30 (61.2%) women, median age: 75.35 years (range: 31–92), were diagnosed of AHPJIs: 22 (44.8%) hips, 26 (53%) knees and 1 (2%) elbow implants. Following total joint replacement our patients had a median infection-free period of 4.9 years (range 0.3 to 18.7). The comorbidities were: 9 (18.3%) rheumatoid arthritis, 7 (14.3%) diabetes, and 6 (12.2%) chronic renal failure. Clinical features were acute in all cases: pain 100%, inflammatory signs 75.5%, and fever 70%. In 27 (55%) of the cases a distant previous infection caused by the same microorganism could be identified. The etiology was: S. aureus 18 (36.7%), streptococcal infections 13 (26.5%), coagulase-negative staphylococci 2 (4%), gram-negative bacilli 11 (22.4%), anaerobes 2 (4%), and mixed infections in 3 (6.1%) cases. Thirty (61.1%) patients underwent early drainage/debridement with retention of the implant, 11 (22.4%) two-stage replacement, 6 (12.5%) arthrodesis, 1 (2.1%) resection arthroplasty, and 1 unknown. Patients were treated with specific AT (median duration of 10.6 weeks) according to the isolated microorganism. At 1 year follow-up 25 (51%) were cured, 7 (14.3%) relapsed after a conservative approach (3 required an arthrodesis and 1 a two-stage replacement), 5 (10.2 %) died and 5 (10.2%) had a re-infection; in 7 the evolution was unknown. AHPJs can be successfully treated in most cases with surgical debridement plus an antibiotic course. If a relapse is observed, removal of the prostheses could be necessary.