Objective: To compare nicotine concentrations and fetal middle cerebral artery resistance indices (RIs) during 21-mg transdermal nicotine use with these values during maternal smoking. Methods: 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. Results: 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). Conclusion: 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.