Nitroglycerin is administered intravenously in acute obstetric emergencies to relax the uterus. However, complications (eg, hypotension, acute uterine bleeding) are frequent, which prompted a search for alternative routes of administration. We hypothesized that the sublingual administration of nitroglycerin would reduce uterine tone and contractility with few complications. Intrauterine pressure was measured in 12 women who were actively laboring (>4 cm dilatation, regular contractions) with epidural analgesia and who were alert and responsive throughout the study. In a double-blind fashion, subjects were randomized to receive either placebo or sublingual nitroglycerin (3 doses, 800 microg each) 10 minutes apart. The obstetric anesthesiologist continuously monitored maternal blood pressure and fetal heart rate. Cervical dilatation was assessed at the beginning and the end of the protocol. The area under the intrauterine pressure curve (integral) was used to estimate uterine contractility. Intrauterine pressure was analyzed before the randomization code was broken. Nitroglycerin did not alter the intrauterine pressure integral after the first dose (placebo, 3147 mm Hg x s [95% CI, 2206-4088] vs nitroglycerin, 4146 mm Hg x s [95% CI, 2451-5841]; P =.22), second dose (placebo, 3123 mm Hg x s [95% CI, 2447-3799] vs nitroglycerin, 3611 mm Hg x s [95% CI, 2723-4499]; P =.28), or third dose (placebo, 3303 mm Hg x s [95% CI, 2616-3990] vs nitroglycerin, 3810 mm Hg x s [95% CI, 2306-5314]; P =.45). Cervical dilation, basal uterine tone, duration and frequency of uterine contractions, or fetal heart rhythm remained unaffected. Maternal mean arterial pressure decreased significantly after nitroglycerin was administered. All women were delivered vaginally without intervention. Three doses of sublingual nitroglycerin (800 microg per dose) reduce neither uterine activity nor tone, despite lowering maternal blood pressure. If a clinical option, sublingual nitroglycerin will require a higher dose, which would place mother and fetus at risk for complication.