To compare nicotine concentrations and fetal middle cerebral artery resistance indices (RIs) during 21-mg transdermal nicotine use with these values during maternal smoking. In this randomized, crossover study, participants smoked approximately 20 cigarettes daily and were between 24 and 36 weeks' gestation. Subjects were randomized to transdermal nicotine or to smoking ad libitum for 8 hours. One week later, they crossed over to the other condition. Maternal plasma nicotine concentrations and hemodynamic measurements were obtained before and after the onset of smoking or patch placement. Area under the plasma nicotine concentration-time curve during patch use was similar to continued smoking (93 versus 89 ng-hour/mL, respectively) (P = .77). The mean (standard error [SE] change in the middle cerebral artery RI from baseline to 4 hours later was similar during patch use and smoking: -.002 (0.008) versus -.02 (0.015), respectively (P = .3). The study had greater than 80% power to detect a 25% difference in nicotine concentrations and a change of 2 standard deviations in the middle cerebral artery RI between conditions. An unexpected finding was that of a loss of fetal heart rate (FHR) reactivity in 5/8 tracings after patch placement versus 1/6 tracings after smoking (P = .12). The baseline FHR increased by a mean (SE) of 8 (4) beats per minute with loss of reactivity in the patch condition, compared with a decrease of 3 (3) beats per minute without loss of reactivity (P = .05). Eight-hour use of 21-mg transdermal nicotine yields nicotine concentrations and middle cerebral artery RIs similar to those produced by hourly smoking in pregnant smokers.