Objectives: We aimed to assess the burden of extended-spectrum b-lactamase (ESBL)-producing Enterobacterales in Swiss long-term care facilities (LTCFs) to describe the molecular epidemiology, describe the intrainstitutional and regional clusters of resistant pathogens, and identify independent institution-and resident-level factors associated with colonization. Design: Cross-sectional study. Setting and Participants: From August to October 2019, we performed a point prevalence study among residents from 16 LTCFs in Western and Eastern Switzerland (8 per region). Methods: Residents underwent screening for ESBL-producing Enterobacterales (ESBL-E); whole-genome sequencing (WGS) was performed. We gathered institution-level (eg, number of beds, staff-resident ratio, alcoholic hand rub consumption) and resident-level [eg, anthropometric data, time in facility, dependency, health care exposure, antibiotic treatment, proton-pump inhibitor (PPI) use] characteristics. Factors associated with colonization were identified using a generalized linear model. Results: Among 1185 eligible residents, 606 (51%) consented to the study. ESBL-E prevalence was 11.6% (70/606), ranging from 1.9% to 33.3% between institutions, with a median of 12.5% in the West and 6.9% in the East (P ¼ .03). Among 59 Escherichia coli (from 58 residents), multilocus sequence type (ST) 131 was most common (n ¼ 43/59, 73%), predominantly its subclone H30R1 (n ¼ 37/43, 86%). WGS data identified multiple intrainstitutional and regional clusters. Independent risk factors for ESBL carriage were previous ESBL colonization [adjusted odds ratio (aOR) 23.5, 95% confidence interval (CI) 6.6-83.8, P < .001), male gender (aOR 2.6, 95% CI 1.5-4.6, P ¼ .002), and use of PPIs (aOR 2.2, 95% CI 1.2-3.8, P ¼ .01). Conclusions and Implications: Overall ESBL-E prevalence in Swiss LTCF residents is low. Yet, we identified several clusters of residents with identical pathogens within the same institution. This implies that particularly affected institutions might benefit from targeted infection control interventions. PPI use was the only modifiable factor associated with carriage of ESBL producers. This study adds to the growing list