OBJECTIVEWe sought to evaluate the role healthcare providers play in carbapenem-resistant Enterobacteriaceae (CRE) acquisition among hospitalized patients.DESIGNA 1:4 case-control study with incidence density sampling.SETTINGAcademic healthcare center with regular CRE perirectal screening in high-risk units.PATIENTSWe included case patients with ≥1 negative CRE test followed by positive culture with a length of stay (LOS) >9 days. For controls, we included patients with ≥2 negative CRE tests and assignment to the same unit set as case patients with a LOS >9 days.METHODSControls were time-matched to each case patient. Case exposure was evaluated between days 2 and 9 before positive culture and control evaluation was based on maximizing overlap with the case window. Exposure sources were all CRE-colonized or -infected patients. Nonphysician providers were compared between study patients and sources during their evaluation windows. Dichotomous and continuous exposures were developed from the number of source-shared providers and were used in univariate and multivariate regression.RESULTSIn total, 121 cases and 484 controls were included. Multivariate analysis showed odds of dichotomous exposure (≥1 source-shared provider) of 2.27 (95% confidence interval [CI], 1.25–4.15; P=.006) for case patients compared to controls. Multivariate continuous exposure showed odds of 1.02 (95% CI, 1.01–1.03; P=.009) for case patients compared to controls.CONCLUSIONSPatients who acquire CRE during hospitalization are more likely to receive care from a provider caring for a patient with CRE than those patients who do not acquire CRE. These data support the importance of hand hygiene and cohorting measures for CRE patients to reduce transmission risk.Infect Control Hosp Epidemiol 2017;38:1329–1334