Because osteomyelitis requires lengthy parenteral antibiotic treatment in patients who are often otherwise healthy, it lends itself well to outpatient parenteral antibiotic therapy (OPAT). Four delivery models for OPAT are (1) self-administration at home, (2) administration by a visiting nurse in the home, (3) infusion center and (4) nursing home. Patient selection is critical to the success of any OPAT program. Clinical and microbiologic data were compiled for more than 500 osteomyelitis patients reported in a registry of OPAT cases in the United States. The most commonly isolated pathogen was Staphylococcus aureus. The antibiotics used most frequently were vancomycin and ceftriaxone. Of 255 patients assessed for bacteriologic outcome, 2 patients developed infection with a new organism and 2 failed to eliminate the causative organism by the end of OPAT therapy. Of 266 patients who were assessed for clinical outcome, 259 improved and 7 failed. Data collected by the OPAT Outcomes Registry confirms that osteomyelitis can be safely and effectively treated with intravenous antibiotics outside the hospital.