Purpose To establish the performance of a multi-parametric test including maternal risk factors and maternal uterine and ophthalmic artery Doppler in the second trimester of pregnancy for the prediction of preeclampsia (PE). Materials and Methods We performed a prospective observational cohort study with pregnant women who underwent a second trimester morphology scan. Maternal uterine and ophthalmic artery Doppler examinations were performed in 415 singleton pregnancies between 18 and 23 weeks of gestation. Additional history was obtained through participant questionnaires, and follow-up occurred to the time of discharge post-delivery. The control and PE groups were compared to continuous variables using the Kruskal-Wallis test and to categorical variables using the Chi-square and Fisher exact tests. Univariate and multivariate logistic regression analyses were performed to determine the best model for the prediction of PE. Results 40 (9.6%) pregnant women developed PE. We observed significant differences in the body mass index (BMI) (p<0.001), parity (p<0.001), mean arterial pressure (MAP) (p<0.001), and pulsatility index (PI) of uterine artery Doppler (p<0.001) between PE and control groups. The best model for the prediction of PE included maternal characteristics, MAP, maternal uterine and ophthalmic artery Doppler with area under receiver operating characteristics (ROC) curve of 0.710 (95% confidence interval, 613-0.807) with a sensitivity of 45% to a false-positive rate of 10% and 35% to a false-positive rate of 5%. Conclusion Maternal ophthalmic artery Doppler did not promote a significant increase in the PE detection rate during the second trimester scan.