© 2021 College of Physicians and Surgeons Pakistan. All rights reserved.Objective: To investigate the efficacy of first-trimester thiol/disulfide homeostasis (t/dh), a new oxidative stress marker, in predicting preeclampsia. Study Design: Prospective cohort study. Place and Duration of Study: Department of Obstetrics and Gynecology, University of Health Sciences, Zeynep Kamil Women and Children Diseases Training and Research Hospital, Istanbul, Turkey, Department of Obstetrics and Gynecology, Bursa Yüksek Ihtisas Training and Research Hospital, Bursa, Turkey, from March 2016 to February 2019. Methodology: In this multi-centre,serum samples of women with839 singleton pregnancies were collected between 11+0 to 13+6gestational weeks. A total of 215 singleton pregnant women were included in the study. The patient group consisted of 38 women, who were diagnosed with preeclampsia; while the control group consisted of 177 healthy pregnant women without any complication during pregnancy and after delivery. Totalthiol (TT) was estimated by the sum of existing thiol groups and reduced thiol groups (S-S and -SH). After the native thiols (-SH) and (TT) were determined, the disulfide (-SS) amounts, disulfide/total thiol percent ratios (-SS/-SH + -SS), disulfide/native thiol percent ratios (-SS/-SH), and native thiol/total thiol percent ratios (-SH/- SH + -SS) were calculated. Results: There were no statistically significant differences between the groups in terms of[(-SH), (TT), (-SS), (-SS/-SH), (-SS/-SH + -SS), and (-SH/-SH + -SS)] six t/dh variables(p>0.05).The first-trimester body mass index (BMI) was statistically different between the two groups (p<0.001). In the receiver operating characteristic curve analysis, none of the concentrations of thiol levels and ratios was found to have a significant predictive value for preeclampsia. The BMI was a significant predictor for preeclampsia (area under curve: 0.749, p<0.001). Conclusion: Maternal serum t/dh at 11+0 to 13+6 weeks of gestation does not predict preeclampsia and t/dh may be the consequence rather than a cause in the pathogenesis of preeclampsia.