To determine the institutional pregnancy complications rate associated with genetic amniocentesis and ascertain whether procedural variables or pre-existing factors may determine an increased risk of having a procedural-related fetal loss, we retrospectively evaluated all the consecutive amniocentesis, with known pregnancy outcome (n = 2990), performed between January 2001 and December 2009 by two very experienced clinicians. The patients who had counselling in the same period but declined to undergo amniocentesis represent the control group (n = 487). A total of 30 fetal losses occurred within 24 weeks' gestation (1%), while in the control group, we had four losses (0.8%). Procedural variables (transplacental sample, multiple needle insertions and gestational age) were not found to be predictive of increased fetal loss rate. Previous vaginal bleeding increased the risk of pregnancy loss after amniocentesis with an OR 4.1 (95% CI 2.0-8.7); on the contrary, a history of two or more miscarriages is not associated with a greater fetal loss rate, while the increased percentage (OR 3.4, 95% CI 1.2-9.0) in patients affected by uterine myoma appears connected, after the comparison with the control group, with the presence of fibroids rather than procedure.