OBJECTIVE Although home parenteral antimicrobial therapy has become common, few studies have carefully examined its adverse effects. METHODS We retrospectively reviewed the medical records of 269 patients who received 291 courses of home parenteral antimicrobial therapy through a hospital-based home infusion program during a 2-year period. Patients with human immunodeficiency virus (HIV) infection were not included. RESULTS The majority (59%) of patients were treated for bone and joint infections. Patients had a mean age of 47 years. The mean duration of antibiotic therapy was 40 days. Of monitored courses, leukopenia occurred in 16%, neutropenia in 7%, thrombocytopenia in 4%, and eosinophilia in 12%, usually after a month of therapy; these adverse effects were most frequently associated with the use of beta-lactam antibiotics. Nephrotoxicity occurred in 8% of monitored courses at a mean of 27 days and was most commonly associated with amphotericin B. Diarrhea occurred in 7% and rash in 4% of patients, and both were most commonly seen with beta-lactam antibiotics. Of those patients with permanent indwelling catheters, 11% of those with central catheters and 9% of those with peripherally inserted central catheters (PICCs) developed line complications. Overall, 8% of patients required rehospitalization. CONCLUSIONS Home infusion antibiotic therapy exposes patients to the complications associated with inpatient antibiotic therapy and needs to be monitored closely to prevent serious complications and rehospitalizations.