Objective To evaluate the screening accuracy of pregnancy hypertensive disorders by maternal serum biomarkers and uterine artery Doppler in the first trimester. Study Design Prospectively enrolled nulliparous women had uterine artery Doppler and serum measured at 11-13 weeks. Maternal characteristics, uterine artery Doppler, and serum placental biomarkers (pregnancy-associated plasma protein-A, Inhibin-A, placental protein 13, A disintegrin and metalloprotease 12, free β-hCG, placental growth factor) were recorded. Results Among 893 women, 20 (2.2%) had gestational hypertension developed and 40 (4.5%) had preeclampsia developed, including 9 (1.0%) early-onset preeclampsia and 16 (1.8%) severe preeclampsia. A combined screening model with clinical characteristics, pregnancy-associated plasma protein-A, Inhibin-A, and placental growth factor could detect 75% of early-onset preeclampsia at a 10% false-positive rate. After adjustment for clinical variables, uterine artery Doppler, placental protein 13, and A disintegrin and metalloprotease 12 did not improve the diagnostic accuracy. Conclusion A combination of clinical characteristics and first-trimester maternal serum biomarkers (pregnancy-associated plasma protein-A, Inhibin-A, and placental growth factor) provides an accurate screening for early-onset preeclampsia in nulliparous women.