Background: Hemoglobinopathies are a major public health problem worldwide. Prevention of thalassemia major can be achieved by population screening in combination with prenatal diagnosis. Prenatal diagnosis of genetic abnormalities necessitates the analysis of fetal material obtained by CVS at 11–13 weeks of gestation or amniocentesis from 16 weeks onwards. An alternative technique for earlier prenatal diagnosis is celocentesis. Aims: The purpose of this study was to evaluate the characteristics of celomic fluid and to establish a laboratory procedure for very early prenatal diagnosis of hemoglobinopathies. Methods: The institutional review board approved the study, which complied with the declaration of Helsinki and the participating couples provided written informed consent. Morre than 600 couples at risk for β-thalassemia or sickle cell disease asked for prenatal diagnosis by celocentesis. The couples were counseled that this technique is offered within the context of research because of limited data on risks and diagnostic accuracy and were advised that it may be preferable for them to undergo conventional prenatal diagnosis (CVS or amniocentesis). Celocentesis was carried out at between 6 + 6 and 9 + 2 weeks. About 1 ml of celomic fluid was sampled from celomic cavity. In presence of high maternal cell contamination, embryo fetal erythroid cells were selectively aspired through micromanipulator. Nested PCR of β-globin gene was analyzed by the direct sequencing method. Results: Celocentesis was successfully performed in all cases,. The volume of CF used for diagnosis was between 450 and 1200 μL. Very low maternal cell contamination was found in 140 samples and unambiguous results were obtained without the need for any preliminary procedures of fetal cells selection. In the other cases the maternal cell contamination was higher 5% and selection of embryo-fetal cells has been necessary. A percentage of 24.5% of fetuses resulted affected by β-thalassemia major or sickle cell/β-thalassemia and women chose to terminate the pregnancy before 10 weeks of gestation. Summary The findings of this study demonstrate that embryo-fetal cell selection from celomic fluid allows reliable and early prenatal diagnosis of hemoglobinopathies. There were no false positive or negative diagnoses. The main advantage of celocentesis, as an alternative to CVS or amniocentesis for invasive prenatal diagnosis, is that it provides earlier diagnosis, at least 4 weeks earlier than what can be achieved by the traditional procedures. This reduces anxiety of parents and provides the possibility for surgical termination of pregnancies, in case of affected fetuses, at 8–10 weeks of gestation, which is less traumatic. Conclusion: Given the low risk of miscarriage, the high rate of feasibility and diagnostic reliability,together with the acceptability of the procedure, is possible to propose celocentesis to at-risk couples for early prenatal diagnosis of hemoglobinopathies.