Women with twin pregnancy are at high risk of spontaneous preterm delivery. Three large randomized trials have shown that progesterone reduces the rate of preterm delivery in high-risk singleton pregnancies, although evidence of significant reduction in perinatal mortality or clear neonatal benefit in singleton women is lacking. The STOPPIT study was a randomized, double-blind, placebo-controlled trial designed to evaluate the potential benefit of progesterone for prevention of preterm birth in women with twin pregnancy. Between 2004 and 2008, 500 women with twin pregnancy were enrolled from 9 antenatal clinics at hospitals in the United Kingdom. At 24 weeks of gestation, the study subjects were randomized to either 90 mg of vaginal progesterone gel (n = 250) or placebo gel (n = 250) daily for 10 weeks. The primary study outcome was delivery or intrauterine death before 34 weeks of gestation. Analysis was performed according to intention to treat. The investigators also performed a meta-analysis of all published and unpublished studies in which women with twin pregnancy were randomly allocated to treatment with a progesterone (including progesterone).No significant difference was found between the 2 groups in the combined proportion of twin pregnancies that resulted in intrauterine death or delivery before 34 weeks (24.7% or 61/247 in the progesterone group vs. 19.4% or 48/247 in the placebo group; odds ratio, 1.36; 95% confidence interval, 0.89-2.09; P = 0.16). The meta-analysis, which included pooled data from 2 studies fulfilling inclusion criteria and data from the present study, confirmed that progesterone does not reduce the risk of early preterm birth or intrauterine death in twin pregnancies (pooled odds ratio, 1.16; 95% confidence interval, 0.89-1.51). No difference between the 2 groups was found in the rate of adverse events.These findings are consistent with previous studies showing that progestogens do not prevent preterm delivery in women with twin pregnancy.