Objective: To investigate whether serum netrin-1 levels measured in hypertensive pregnant women could predict the development of early-onset preeclampsia (EOP). Methods: This prospective observational study was conducted at a single academic medical center between August 1, 2019, and July 31, 2021. The study included patients aged >18 years who presented to our clinic because of gestational hypertension at gestational weeks 20–24 and underwent serum netrin-1 level measurements. All the patients were followed up until delivery for the development of preeclampsia. The patients were divided into two subgroups: those who developed EOP and those who developed late-onset preeclampsia (LOP). Results: Ninety-seven patients and 45 healthy controls were included in the study. EOP and LOP developed in 43 (44.3%) and 54 (55.7%) of the patients, respectively. The mean serum netrin-1 level at the time of presentation was significantly higher in the EOP group than in the control group (916.8 ± 370.5 pg/mL vs 487.7 ± 220.4 pg/mL; p < 0.001). A multivariate logistic regression analysis revealed that high serum netrin-1 level (odds ratio: 6.02, 95% confidence interval [CI]: 2.45–18.20, p = 0.001) was an independent predictor of EOP. Serum netrin-1 levels >784.9 pg/mL predicted the development of EOP with a sensitivity of 72.0% (95% CI: 56.3–84.7%) and specificity of 88.8% (95% CI: 75.9–96.3%). Conclusion: High serum netrin-1 levels were significantly associated with the development of EOP. The initial serum netrin-1 level may be useful for determining the risk of developing EOP in women with gestational hypertensive disorder.