tudy Objective Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used, and unfortunately, readmissions during OPAT are common. The purpose of this study was to identify predictors of hospital readmission among patients receiving OPAT. Design Retrospective cohort study. Setting Large academic tertiary care hospital. Patients A total of 216 adults who were discharged and received OPAT through a peripherally inserted central catheter for at least 2 days for treatment of an active infection, excluding patients with cystic fibrosis, between January 2012 and August 2013. Of these patients, 43 had hospital readmissions and 173 did not. Measurements and Main Results The median age of all study patients was 56 years. Common infections included bone and joint (32%), genital/urinary tract (16%), endocarditis (14%), central nervous system (9.7%), and pneumonia (9.7%). For the 43 patients (20%) who had readmissions, reasons for readmission were infection recurrence or progression (33%), adverse drug reactions (24%), central catheter–associated issues (16%), or non-OPAT–related reasons (27%). In the multivariate analysis, patients assigned to a primary care physician were less likely to be readmitted (odds ratio [OR] 0.286, 95% confidence interval [CI] 0.115–0.711), whereas factors independently associated with an increased readmission rate included previous hospital admission in the past 12 months (OR 2.588, 95% CI 1.159–5.778), medical history of malignant lymphoma (OR 25.172, 95% CI 2.311–272.209), and increased planned OPAT duration (OR 1.058, 95% CI 1.034–1.082). Conclusion Readmissions while patients received OPAT were common. Therefore, proactive interventions including primary care physician assignment to facilitate follow-up and communication should be implemented to decrease the risk of readmission, particularly in the identified high-risk populations.