OBJECTIVE: To determine if high-dose oxytocin reduces the need for additional uterotonic agents at cesarean. METHODS: A randomized, double-masked trial of two oxytocin regimens was performed to prevent postpartum uterine atony in laboring women. The pharmacy prepared sequentially numbered oxytocin solutions containing either 10 U/500 mL or 80 U/500 mL of lactated Ringer's solution infused over 30 minutes after cord clamping. The need for additional uterotonic agents was determined by the surgical team. Hypotension was diagnosed and treated with crystalloid or a pressor agent. To detect a 50% decrease in the need for additional uterotonic agents and considering a β error of 0.2, 220 patients would be required in each group (α = 0.05, two-tailed x2 test). RESULTS: The low-dose group (n = 163) received 333 mU/min, and the high-dose group (n = 158) received 2667 mU/min of oxytocin. The groups were similar with respect to risk factors for atony. Women in the low-dose group received additional uterotonic medication significantly more often than those in the high-dose group (39% compared with 19%, P < .001, relative risk 2.1, 95% confidence interval 1.4, 3.0). Moreover, more women in the low-dose group received methylergonovine, 15-methyl prostaglandin F2α or both (9% compared with 2%, relative risk 4.8, 95% confidence interval 1.4, 16) after additional oxytocin (median 20 U) had been added to the study solution. The incidence of hypotension was similar in both groups. CONCLUSION: Compared with an infusion rate of 333 mU/min, oxytocin infused at 2667 mU/min for the first 30 minutes postpartum reduces the need for additional uterotonic agents at cesarean delivery. © 2001 by the American College of Obstetricians and Gynecologists.