Introduction: Standard therapy for orthopedic device infections includes a two-stage exchange and prolonged antimicrobial therapy. In a subgroup of patients, retention of the device seems to be an effective alternative. Methods: In a prospective study we evaluated treatment efþcacy of orthopedic device infections with implant retention. Inclusion criteria were: early manifestation, stable implant, known pathogen, susceptibility of staphylococci to quinolones and rifampin, good condition of soft tissue. Initially, intravenous antimicrobial therapy was given for 2 weeks, followed by oral treatment for 10 weeks (knee prostheses for 6 months). Results: From January 1999 through June 2002, 19 patients were included: hip prosthesis (9), knee prostheses (6) and internal þxation devices (4). Isolated pathogens were: staphylococci (14), streptococci (4), enterococci (1), and Propionibacterium acnes (1). Open debridement with device retention was performed in 13 patients; the remaining 6 patients were treated with antibiotics only. After initial 2-week intravenous therapy, staphylococcal infections were treated with oral ciproßoxacin 750 mg bid + rifampin 450 mg bid, streptococcal and enterococcal infections with oral amoxicillin 750 mg tid and the P. acnes-infection with oral clindamycin 600 mg tid. 12 of 16 patients were followed for at least 24 months. 10 (83%) had no symptoms or signs of infection at follow-up, 2 (17%) had a relapse Conclusion: In carefully selected patients, device retention with antimicrobial treatment for 3–6 months may be an effective approach.