Background: In Dutch hospitals a six-point questionnaire is currently mandatory for risk assessment to identify carriers of multidrug-resistant organisms (MDROs) at the time of hospitalization. Presence of one or more risk factors is followed by pre-emptive isolation and microbiological culturing. Aim: To evaluate the yield of the universal risk assessment in identifying MDRO carriers upon hospitalization. Methods: A cross-sectional study was performed using routine healthcare data in a Dutch tertiary hospital between January 1 st, 2015 and August 1 st, 2019. MDRO risk assessment upon hospitalization included assessment of: known MDRO carriage, previous hospitalization in another Dutch hospital during an outbreak or a foreign hospital, living in an asylum centre, exposure to livestock farming, and household membership of a meticillin-resistant Staphylococcus aureus carrier. Findings: In total, 144,051 admissions of 84,485 unique patients were included; 4480 (3.1%) admissions had a positive MDRO risk assessment. In 1516 (34%) admissions microbiological screening was performed, of which 341 (23%) yielded MDRO. Eighty-one patients were categorized as new MDRO carriers, as identified through MDRO risk assessment, reflecting 0.06% (95% confidence interval: 0.04–0.07) of all admissions and 1.8% (1.4–2.2) of those with positive risk assessment. As a result, the number of ‘MDRO risk assessments needed to perform’ and individual ‘MDRO questions needed to ask’ to detect one new MDRO carrier upon hospitalization were 1778 and 10,420, respectively. Conclusion: The yield of the current strategy of MDRO risk assessment upon hospitalization is limited and it needs thorough reconsideration.