The East Flanders Prospective Twin Survey (EFPTS) is a prospective, population-based registry of multiple births in the province of East-Flanders, Belgium. EFPTS has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are recruited at birth; basic perinatal data recorded; chorion type and zygosity established; and since 1969 placental biopsies have been taken and frozen at −20 °C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic–diamnionic pairs (early, with splitting before the fourth day after fertilization), the monochorionic–diamnionic pairs (intermediate, splitting between the fourth and the seventh day post-fertilization), and the monochorionic–monoamnionic pairs (late, splitting after the eighth day post-fertilization). Studies can be initiated taking into account primary biases, those originating ‘in utero’. Such studies could throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events, and the gene–environment interactions as far as periconceptional and intrauterine environment are concerned.