<p>This study aimed to evaluate the predictive value of serum transthyretin levels in conjunction with uterine artery Doppler ultrasound during the first trimester for predicting preeclampsia. We conducted a prospective observational study at King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Chulalongkorn University, Bangkok, Thailand. The study involved singleton pregnant women undergoing a first-trimester screening at a gestational age of 11–13^+ 6 weeks. We measured maternal serum transthyretin levels and performed transabdominal uterine artery Doppler studies (mean pulsatility index, diastolic notching). Pregnancy outcomes were recorded, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the tests were calculated. The primary outcome was the sensitivity of serum transthyretin levels in conjunction with uterine artery Doppler ultrasound for predicting preeclampsia. The secondary outcomes were the specificity, PPV, and NPV of the tests. A total of 372 patients were analyzed, with preeclampsia occurring in 30 cases. Serum transthyretin levels were significantly lower in women with preeclampsia compared to those without (2.8 ng/ml vs. 7 ng/ml, <i>p</i> &lt; 0.001). The mean pulsatility index of the uterine artery and the presence of diastolic notching did not significantly differ between the groups. Using a cut-off value of less than 0.5 multiples of the median for gestational age, the sensitivity, specificity, PPV, and NPV for predicting preeclampsia were 76.7%, 75.1%, 21.3%, and 97.4%, respectively. Furthermore, when combining abnormal transthyretin levels with abnormal uterine artery pulsatility index, the sensitivity was 76.7%, specificity 71.9%, PPV 19.3%, and NPV 97.2%. The combination of serum transthyretin and first-trimester uterine artery Doppler ultrasound was effective for predicting preeclampsia. Serum transthyretin may serve as a promising biomarker for early prediction of preeclampsia.</p>