The investigation reviewed the experience of a single institution using outpatient parenteral antibiotic therapy with daptomycin as monotherapy. After institutional review board approval, patients discharged from Baystate Medical Center on daptomycin as monotherapy were investigated for clinical outcome. The authors present their data descriptively comparing the success rates of daptomycin therapy according to clinical factors. Thirty-three persons were included, and all of them survived during the therapy. All patients received 6 to 8 mg/kg/day of daptomycin administered over 30 minutes, were treated between 2 to 8 weeks and received 74% to 90% of therapy after hospital discharge. Ninety-four percent of patients studied were clinically cured. Thirty-three percent of patients with osteomyelitis required surgery for cure, but all successfully completed treatment. Twelve percent had complications that did not alter treatment course. No elevations of creatine phosphokinase were noted; however, this was inconsistently checked. These results indicate that outpatient parenteral antibiotic therapy using daptomycin is a suitable agent for patients with selected Gram-positive bacterial infections. After a relatively brief hospitalization, the majority of patients can complete at least three fourths of total treatment duration outside of the hospital.