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Management of noncephalic second twin delivery rests on the results of population-based retrospective studies of twin births that have shown higher neonatal mortality and morbidity for second twins with noncephalic, compared with cephalic, presentations after vaginal delivery of the first twin. Because these studies are flawed by data of questionable validity, do not report the obstetrical practices at delivery, and do not allow collection of potential confounding variables, we performed a national prospective study specially designed to evaluate the management of twins' delivery.We sought to assess neonatal mortality and morbidity according to second twin presentation after vaginal birth of the first twin.The Jumeaux Mode d'Accouchement study was a nationwide prospective population-based cohort study of twin deliveries performed in 176 maternity units in France from February 2014 through March 2015. The primary outcome was a composite of intrapartum mortality and neonatal mortality and morbidity. Neonatal outcomes of second twins born ≥32 weeks of gestation after vaginal delivery of the first cephalic or breech twin were compared according to the noncephalic or cephalic second twin presentation. Multivariable logistic regression models controlled for potential confounders. Subgroup analyses were conducted according to the breech or transverse presentation of the noncephalic second twin, and gestational age at delivery, before or after 37 weeks of gestation.Among 3903 second twins enrolled in the study, 2384 (61.1%) were in cephalic and 1519 (38.9%) in noncephalic presentations, of whom 999 (25.6%) were in breech and 520 (13.3%) in transverse presentation. Composite neonatal mortality and morbidity did not differ between the noncephalic and cephalic group (47/1519 [3.1%] vs 59/2384 [2.5%]; adjusted odds ratio, 1.23; 95% confidence interval, 0.81–1.85). No significant difference between groups was shown for the primary outcome in subgroup analyses according to type of noncephalic second twin presentation or gestational age at delivery. Cesarean delivery rates for the second twin were lower in the breech than in the cephalic group (14/999 [1.4%] vs 75/2384 [3.1%], P = .003) and lower in the cephalic than in the transverse group (75/2384 [3.1%] vs 35/520 [6.7%], P < .001).Noncephalic and cephalic second twin presentations after vaginal delivery of the first twin ≥32 weeks of gestation are associated with similar low composite neonatal mortality and morbidity. Vaginal delivery of noncephalic second twin is a reasonable option.