Intestinal colonization with multidrug-resistant Enterobacterales (MDRE-IC) increases the risk of MDRE bloodstream infection (BSI). However, its impact on the overall risk of nosocomial Enterobacterales bloodstream infections (nE-BSIs) remains unclear. This study aimed to determine this risk and identify associated factors in hospitalized patients.This retrospective cohort study at a 3200-bed tertiary institution including patients hospitalized in 2019 who underwent MDRE rectal swab (RS) screening. Inclusion criteria were age ≥18 years, first RS in 2019, follow-up ≥7 days, and Enterobacterales BSIs >48 hours after RS. The primary outcome was the first nE-BSI during the follow-up period, analyzed using a Cox model.Among 7006 patients, 817 (11.9%) had MDRE-IC. Most were male and primarily hospitalized in acute wards. nE-BSIs occurred in 433 (6.1%) patients and were more frequent in patients with MDRE-IC than the non-colonized group (adjusted hazard ratio [aHR] = 1.78, 95% confidence interval [CI]: 1.40-2.26). Intestinal colonization with extended-spectrum β-lactamase-producing and carbapenemase-resistant Enterobacterales showed similar risks for Enterobacterales BSI onset: aHR = 1.73 (95% CI: 1.33-2.24) and aHR = 2.02 (95% CI: 1.27-3.22), respectively.In hospitalized patients, MDRE-IC is associated with a higher rate of nE-BSI than those without MDRE-IC, underscoring the urgent need for improved infection prevention and control measures, as well as optimized antibiotic use to mitigate this risk.