The incidence of preterm delivery has been increasing, and our aim was to estimate the influence of fetal sex on the risk of preterm delivery in dichorionic twins after spontaneous conception. Methods: 125 spontaneously conceived dichorionic twin gestations, with viable fetuses, born after 24 weeks and delivered spontaneously before 37 weeks, were enrolled. The impact of fetal sex, previous preterm delivery, maternal age, body-mass-index, smoking, and parity on gestational age at birth were evaluated. Results: Despite similar baseline characteristics in all three groups, women with one or two male fetuses delivered significantly more often before 34 weeks than patients with two female fetuses, 48% (23/48) and 43% (19/44) vs 21% (7/33), p = .04. Regression analyses, including fetal sex, maternal age, maternal body-mass-index, smoking, previous preterm delivery and parity, revealed that only fetal sex was significantly associated with spontaneous preterm delivery (p = .03). Conclusion: Fetal sex appears to be a risk factor for preterm delivery in spontaneously conceived dichorionic twin gestations. Twin pregnancies with one or two male fetuses seem to be at higher risk for spontaneous preterm delivery than those with only females.Keywords: fetal sex, preterm birth, spontaneous conception, chorionicity, twin pregnancy Despite improvements in medical care, the incidence of preterm delivery, defined as birth before 37 weeks of pregnancy, has increased (Alexander & Slay, 2002;Goldenberg, 2002;Moutquin, 2003;Slattery & Morrison, 2002;Roberts et al., 2002). Preterm delivery is still the leading cause of perinatal mortality and morbidity in industrialized countries, accounting for 28% of neonatal mortality worldwide (Guyer et al., 1997;Menon, 2008). Nearly 50% of all children born before 26 complete weeks of gestation are severely disabled (Wood et al., 2000).Though the pathophysiology of preterm delivery remains to be elucidated, data from animal experiments indicate that fetal gender could play a role in the etiology of preterm delivery (Challis et al., 2000). Epidemiological studies in humans appear to affirm these observations, reporting a higher rate of male fetuses among preterm deliveries (Astolfi et al., 1999;Zeitlin et al., 2002). Brettell et al., for instance, report that male singletons are more likely to deliver preterm when compared to females, particularly because of higher incidence of preterm labor and premature preterm rupture of membranes (PPROM) (Brettell et al., 2008). While some authors have attributed the higher risk of preterm delivery in male fetuses to higher weights of males at lower gestational ages compared to females, others have suggested possible immunological causes (Di Renzo et al., 2007;Gleicher, 2008;McGregor et al., 1992).What causes labor is still, in principle, unknown (Muglia & Katz, 2010). Among many possible suggestions, Gleicher recently suggested that labor may be the consequence of a programmed, immunologically induced, graft-versus-host disease (GVHD) -like process, in which t...