Pregnant women with preeclampsia have been found to have elevated cerebral perfusion pressure and impaired cerebral autoregulation compared with normal pregnant women. Transcranial Doppler is a noninvasive technique used to estimate cerebral perfusion pressure. The effects of different antihypertensive medications on cerebral perfusion pressure in preeclampsia are unknown. To compare the change in cerebral perfusion pressure before and after intravenous labetalol vs oral nifedipine in the setting of acute severe hypertension in pregnancy. This is a prospective cohort study of pregnant women between 24 and 42 weeks' gestation with severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg). Women who consented to the study and received either intravenous labetalol or oral nifedipine were included. Exclusion criteria included active labor or receipt of any antihypertensive medication within 2 hours of initial cerebral perfusion pressure measurement. Peripheral blood pressure and transcranial Doppler studies for middle cerebral artery hemodynamics were performed prior to the administration of antihypertensive medications and repeated 30 minutes after medication administration. A total of 16 women with acute severe hypertension were enrolled; 8 received intravenous labetalol and 8 received oral nifedipine. There were no significant differences between the labetalol and nifedipine groups in baseline characteristics such as maternal age, race and ethnicity, payment, hospital site, body mass index, nulliparity, gestational age, preexisting diabetes mellitus or chronic hypertension, fetal growth restriction, magnesium sulfate administration, and symptomatology (P>.05). When examined 30 minutes after the administration of either intravenous labetalol or oral nifedipine, there was a significantly greater decrease in systolic blood pressure (-9.8 mm Hg vs -39 mm Hg; P=.003), mean arterial pressure (-7.1 mm Hg vs -22.3 mm Hg; P=.02), and cerebral perfusion pressure (-2.5 mm Hg vs -27.7 mm Hg; P=.01) in the nifedipine group. There was no statistically significant decrease in diastolic blood pressure (-12.9 mm Hg vs -5.4 mm Hg; P=.15). The change in middle cerebral artery velocity by transcranial Doppler was compared between the groups and was not different (0.07 cm/s vs 0.16 cm/s; P=.64). Oral nifedipine resulted in a significant decrease in cerebral perfusion pressure, whereas labetalol did not, after administration for acute severe hypertension among women with preeclampsia. This decrease seems to be driven by a decrease in peripheral arterial blood pressure rather than a direct change in cerebral blood flow.