ABSTRACT Over 1 million women have their labor induced in the United States each year, and synthetic oxytocin infusion is the most common method used. However, compared to spontaneous labor, medical induction is resource- intensive, has increased obstetric risks, and is associated with less successful breastfeeding. In contrast to endogenous oxytocin hormone which is released in a pulsatile fashion in the brain, synthetic oxytocin is continuously infused intravenously, resulting in important limitations related to efficacy, safety, and cost. Akin to spontaneous labor contractions, infant suckling of the breast nipple is known to stimulate the pulsatile release of endogenous oxytocin from the posterior pituitary gland. Nipple stimulation therapy via electric breast pump similarly stimulates endogenous oxytocin release, and our preliminary work shows that it is a feasible and acceptable inpatient method that results in a desirable uterine contraction patter n in nulliparas. Our pilot study of 100 randomized nulliparas showed that intrapartum nipple stimulation therapy decreases labor duration and trends toward a significant increase in the rate of spontaneous vaginal delivery compared to synthetic oxytocin infusion. Further, nipple stimulation reduced the dose and duration of synthetic oxytocin even when adjunctive synthetic oxytocin was used. Therefore, nipple stimulation therapy will likely prove to be an efficacious labor induction method that increases the likelihood of spontaneous vaginal delivery, and also have added physiologic benefits. For example, nipple stimulation triggers lactation by inducing the milk ejection reflex, and our preliminary work also shows that nipple stimulation therapy via electric breast pump results in early colostrum production and milk letdown in the majority of women, including first-time mothers. Earlier lactation would alleviate the most common reasons for early breastfeeding discontinuation by improving maternal perception of insufficient milk supply and the severity of weight loss that occurs in infants in the first few days of life as they establish feeding. This in turn would improve the likelihood of sustained breastfeeding for the recommended 6 months, which also has many short- and long-term benefits. Consequently, nipple stimulation therapy during labor has tremendous potential public health and cost benefits, and its success would be particularly important in areas of poverty, including developing countries. We propose a multicenter randomized trial at Yale and Northwestern Universities to compare inpatient nipple stimulation therapy via electric breast pump versus immediate synthetic oxytocin infusion without nipple stimulation for nulliparous women undergoing labor induction. This trial of 988 nulliparous women will provide adequate statistical significance to detect clinically meaningful differences in delivery mode and breastmilk as the sole source of nutrition for newborns. Successful completion of...