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For a pregnant woman considering prenatal screening for early detection of Down Syndrome (DS), there are at least two major outcomes of interest: undetected DS live births and euploid procedure-related fetal losses. The risk-cutoff value of 1/270 has been commonly used for recommending a diagnostic test. The objective of this study was to assess the impact of women's preferences for different pregnancy outcomes on the optimal risk-cutoff values for integrated screening.We built a Monte Carlo simulation model of 100 000 singleton second-trimester pregnancies to assess the probabilities of DS live births and euploid procedure-related fetal losses for various risk-cutoff values. To capture how undesirable some women may view an undetected DS live birth relative to a euploid procedure-related fetal loss, we used a ratio W1 : W2 of weights (penalties) assigned to these two adverse pregnancy outcomes.As the relative weight changes, the optimal risk-cutoff value changes significantly.A one-size-fits-all risk-cutoff value, such as 1/270, may not always be the best choice, depending on the preferences of women. Preference-sensitive risk-cutoff values for DS screening have the potential to improve the pregnancy outcomes and patient satisfaction.