Objective To determine if decreased resistance (vasodilatation) in the maternal middle cerebral artery (MCA) in the second trimester can predict third-trimester development of pre-eclampsia. Methods Four-hundred and five low-risk gravidas had MCA transcranial Doppler (TCD) once in the second trimester. Maternal/neonatal outcomes were evaluated after delivery. Mean blood pressure, MCA velocities, resistance index (RI), pulsatility index (PI) and cerebral perfusion pressure (CPP) were compared between normotensive and pre-eclamptic cohorts. Results Seven subjects (1.7%) developed pre-eclampsia. An RI of <0.54 and a PI of <0.81 were clinically useful in predicting subsequent pre-eclampsia. Areas under the receiveroperating characteristics curves for RI and PI were 0.93 and 0.93, respectively, with optimal sensitivity and specificity of 86% and 93% for both variables. Positive and negative likelihood ratios were 11.8/0.15 (RI) and 12.3/0.15 (PI). Conclusion TCD indices of low maternal MCA resistance in the second trimester are predictive of the subsequent development of pre-eclampsia in a low-risk, ethnically homogeneous population. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons, Ltd.