- Objective To evaluate whether vanishing twin syndrome (VTS) is associated with adverse perinatal outcome. Design A retrospective cohort study investigating the impact of VTS on perinatal outcome was conducted. Parturients were classified into three groups: those pregnancies that started with double fetal sacs and spontaneously reduced into one (VTS), those with dichorionic twins, and those with singleton pregnancies. Statistical analysis included multiple logistic regression models to control for possible confounders. Setting Tertiary university medical center. Patient(s) The study involved 252,994 singleton deliveries between the years 1988 and 2012. Intervention(s) None. Main Outcome Measure(s) The impact of VTS on perinatal outcome. Result(s) During the study period, 278 pregnancies with VTS were compared with 1,801 pregnancies of dichorionic twins and 252,994 pregnancies of singletons. A significant linear association was documented among the three groups and various adverse outcomes, including gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), very low birth weight (VLBW), and perinatal mortality. The higher risk was noted in the VTS group, and the lowest in singletons. Using multivariable logistic regression models, while controlling for confounders such as fertility treatment and maternal age, VTS (as compared with singletons) was found to be an independent risk factor for several adverse perinatal outcomes including GDM, IUGR, VLBW, low Apgar scores, and perinatal mortality (adjusted odds ratios with their respective 95% confidence intervals, 1.4 [1.01–2.0], 2.7 [1.7–4.3], 6.9 [4.7–10.2], 1.9 [1.1–3.3], 2.4 [1.2–4.5]). Conclusion(s) Pregnancies with VTS are associated with an adverse perinatal outcome, even after controlling for confounders such as fertility treatment and maternal age.