The aim of the present study was to identify a subset of patients at high risk of multiple birth after IVF and hence suitable for one-embryo transfer, which undoubtedly would reduce the multiple birth rate. This retrospective study included 2107 IVF cycles in which two embryos were transferred. Factors with possible correlation to multiple birth were studied in a multivariate analysis. The factors included background data (female age, previous pregnancies and births, previous IVF cycles, indication for IVF) and IVF cycle characteristics. The following factors were independently predictive of multiple birth: female age expressed a negative correlation while number of good quality embryos transferred was positively correlated. A subset of patients was identified as being at high risk of multiple birth by including age, cycle number and presence of tubal infertility in a model derived from a logistic regression analysis. The rate of multiple births can be reduced from 26% to 13% of all births if one-embryo transfer is performed in selected cases. The total birth rate will decrease from 29% to 25% but may be completely restored by performing one additional one-embryo freeze transfer in high risk patients who do not achieve a term pregnancy.