Living in high-endemic regions increases the risk of intestinal colonization by multidrug-resistant Enterobacterales (MDR-Ent). This study investigated Swiss expatriates residing abroad (≥ 3 months) to assess their colonization status upon returning to Switzerland. Selective culture-based methods were implemented to detect third-generation cephalosporins- (3GC-R), carbapenems- (CR), and colistin-resistant (COL-R) strains. Whole-genome sequencing was used to characterize antimicrobial resistance genes, sequence type (ST), and phylogroup of MDR-Ent. Epidemiological data were analyzed using uni- and multivariable models to identify risk factors, providing crude and adjusted odds ratios (ORs). Among 196 participants living across Africa, Asia, the Americas, and Europe, the overall MDR-Ent colonization prevalence was 42.9%. Continent of residence emerged as a significant risk factor (p = 0.04) for colonization: Africa (adjusted OR = 3.4, 95% CI 1.0-11.0) and Asia (adjusted OR = 4.7, 95% CI 1.5-15.0). Extended-spectrum β-lactamase-producing Escherichia coli (Ec) was the most frequent isolated species (n = 107 out of 119 Ent). Most 3GC-R-Ec possessed bla