OBJECTIVE To determine incidence of and risk factors for readmissions with multidrug-resistant organism (MDRO) infections among patients with previous MDRO infection. DESIGN Retrospective cohort of patients admitted between January 1, 2006, and October 1, 2015. SETTING Barnes-Jewish Hospital, a 1,250-bed academic tertiary referral center in St Louis, Missouri. METHODS We identified patients with MDROs obtained from the bloodstream, bronchoalveolar lavage (BAL)/bronchial wash, or other sterile sites. Centers for Disease Control and prevention (CDC) and European CDC definitions of MDROs were utilized. All readmissions ≤1 year from discharge from the index MDRO hospitalization were evaluated for bloodstream, BAL/bronchial wash, or other sterile site cultures positive for the same or different MDROs. RESULTS In total, 4,429 unique patients had a positive culture for an MDRO; 3,453 of these (78.0%) survived the index hospitalization. Moreover, 2,127 patients (61.6%) were readmitted ≥1 time within a year, for a total of 5,849 readmissions. Furthermore, 512 patients (24.1%) had the same or a different MDRO isolated from blood, BAL/bronchial wash, or another sterile site during a readmission. Bone marrow transplant, end-stage renal disease, lymphoma, methicillin-resistant Staphylococcus aureus, or carbapenem-resistant Pseudomonas aeruginosa during index hospitalization were factors associated with increased risk of having an MDRO isolated during a readmission. MDROs isolated during readmissions were in the same class of MDRO as the index hospitalization 9%-78% of the time, with variation by index pathogen. CONCLUSIONS Readmissions among patients with MDRO infections are frequent. Various patient and organism factors predispose to readmission. When readmitted patients had an MDRO, it was often a pathogen in the same class as that isolated during the index admission, with the exception of Acinetobacter (~9%). Infect Control Hosp Epidemiol 2018;39:12-19.