Objective: To assess ability of first and second trimester Placental Vascularization Indices (PVIs) to predict pre-eclampsia (PE) in high-risk pregnancies. Method: PVIs derived from 3-Dimensional power Doppler imaging were measured at 11+0–13 + 6 (n = 194) and 19+0–21 + 6 weeks (n = 195). Logistic regression (LR) models used PE as the outcome. To quantify added value of PVIs to baseline characteristics in predicting PE, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices were calculated. Results: Overall rate of PE was 12% (n = 26). Lower first trimester PVIs were seen in women with PE (mean, SD); Vascularization Index (VI,%): 10.0 (6.2) v 14.7 (7.6), P = 0.005, Flow Index (FI): 37.7 (9.1) v 42.9 (10.4), P = 0.03, Vascularization Flow Index (VFI): 3.8 (2.5) v 6.6 (4.0), P < 0.001). All first trimester PVIs predicted PE in LR models adjusted for covariates. IDI and NRI analyses confirmed added clinical utility of VI (IDI 0.05, P = 0.004; NRI 0.66, P < 0.001) and VFI (IDI 0.06, P = 0.004; NRI 0.53, P = 0.91). In the second trimester, FI was lower in women with PE (39.6 (9.1) v 44.4 (8.6), P = 0.01) and predicted PE in adjusted LR models (standardised OR 0.53, 95% CI 0.29–0.97, P = 0.04). FI discriminated between cases and non-cases of PE (IDI 0.04, P = 0.04). Conclusion: First trimester placental vascularization indices (VI, FI and VFI) have the potential to predict PE in high-risk pregnancies, with FI remaining predictive in the second trimester.