Objectives: We aimed to establish the earliest gestational age at which fetal DNA in maternal plasma could be detected and whether this was reliable at 12-13 weeks' gestation. Study design: A prospective observational cohort study of 32 pregnancies either after IVF or before prenatal diagnosis by CVS. Maternal blood was taken and RT-PCR was carried out to detect the multi-copy Y chromosome associated DSY14 gene. The end point was gender as assessed at delivery or on karyotype. Results: Y signal was obtained as early as 14 days post conception (4 weeks' gestation) and has a good prediction rate by 12 weeks' gestation. Conclusion: Free fetal DNA allows very early prediction of fetal sex in some cases and could be useful for clinical use for X-linked conditions by the end of the first trimester.