BACKGROUND: Extended spectrum beta-lactamase producing enterobacteriaceae (ESBL-E) are increasing worldwide, but there is sparse data on patient-to-patient transmission and the prevalence among risk groups in Switzerland. A prospective, observational cohort study was performed to: 1) assess the prevalence of ESBL-E at admission among at-risk groups; 2) evaluate nosocomial cross-transmission in acute care (ACF) versus long-term care facilities (LTCF); and 3) evaluate prevalent mutations of the detected beta-lactamase genes. METHODS: Predefined risk groups were screened either on admission or after having been in contact with index patients diagnosed with ESBL-E by clinical cultures. Three patient categories were distinguished: patients previously known to be ESBL-E carrier (category I); patients transferred from countries with known high ESBL-E prevalence and thus at risk for ESBL-E carriage (category II); and roommates of index patients (category III). RESULTS: A total of 93 patients with ESBL-E were identified: Sixty-two percent (31/50) of category I patients were positive when screened upon rehospitalisation (category I); eighteen percent (22/124) of category II patients; and eight out of 177 category III patients (4.5%) of which five showed identical ESBL-E strains or shared the same beta-lactamase gene as their index cases. The incidence density of transmission was 0.9/1000 exposure-days, with more transmissions in ACF than in LTCF (4.2 vs 0.4/1000 exposure days). CTX-M-15 was the predominant beta-lactamase gene (60%) among the index patients. CONCLUSIONS: The prevalence of ESBL-E carriage among patients coming from regions with endemic rates or those previously identified as carriers is high; on-admission screening should be considered for these high risk populations. Documented nosocomial ESBL-E transmission was low.