Preterm birth before 37 weeks’ gestational age complicates more than 12% of pregnancies. Tocolytic therapy is intended to reduce neonatal deaths and illness by delaying birth, but current tocolytic agents are not very effective and, despite prolonging pregnancy, have failed to improve infant outcomes. There is evidence from both animal and human studies that glyceryl trinitrate (GTN, nitroglycerin) achieves tocolysis with few serious side effects. This multicenter Canadian trial enrolled 153 women in labor at 24-32 weeks’ gestation, based on 4 or more painful uterine contractions every 20 minutes and cervical change. Seventy-four women were randomized to receive a transdermal GTN patch, and 79 to receive a placebo patch. An additional patch was applied if uterine activity continued after 60 minutes and, after 24 hours, all patches were replaced with the same number for 24 hours longer. Patches were removed after 48 hours. The primary outcome was a composite of neonatal mortality and morbidity, the latter including chronic lung disease, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis. Baseline characteristics were comparable in the intervention and control groups. Treatment with GTN reduced the primary composite outcome significantly (relative risk [RR], 0.29; 95% confidence interval [CI], 0.08, 1.00). The risk difference was −0.10 (95% CI, −0.19, −0.01). The number needed to treat was 10 (95% CI, 5, 100). Births before 28 weeks’ gestational age were reduced, although not significantly (RR, 0.50; 95% CI, 0.23, 1.09). Pregnancies were prolonged by 7.2 days on average in the GTN group, also not a statistically significant change. Women given GTN had significantly more side effects (RR, 1.41; 95% CI, 1.06, 1.86). The commonest problem was headache, but in most cases it was not necessary to remove the patches. The investigators conclude that, in view of the substantial health care and societal costs of neonatal morbidity, treating women in preterm labor with transdermal GTN may yield major cost savings and longer-term health benefits.