Responsible pathogens of chronic bone infections (CBI) are frequently resistant, requiring parenteral antimicrobial therapy. Therefore, adverse effects may be observed. We have determined the rate of adverse effects of antimicrobial therapy for CBI in a retrospective study of all patients receiving parenteral drugs via an implantable port. Patients from one medical ward (n = 89) and from one surgical ward (n = 40) between January 1995 and December 2005 were included in this study. The CBI included were 85 osteomyelitis (66%) and 44 prosthetic joint infections (34%). The main group of pathogens was gram positive cocci (n = 144; 65%). The total duration of antibiotic treatment was 205 +/- 200 days, including 133 +/- 100 days for parenteral therapy. Thirty-three catheter-related complications were observed in 27 patients (21%). All complications led to hospitalization but none led to death. Twenty-one antibiotic-related complications occurred in 18 patients (16%), and one allergic reaction led to death. The mean duration of follow-up was 290 days. Remission was observed in 84 patients (65%). In multivariate analysis, adverse effects were mostly observed in the medical department. Adverse effects affect at least one third of the patients treated for CBI with parenteral antimicrobial therapy and are related to both the implantable port and the antibiotic compounds.