OBJECTIVE: To estimate an institution's specific fetal loss rate after a second-trimester genetic amniocentesis. METHODS: This is a retrospective cohort study using our prenatal diagnosis database for all pregnant women presenting for care between 1990 and 2006. We compared the fetal loss rate in women who underwent amniocentesis between 15 and 22 weeks of gestation with those women who did not have any invasive procedure and had a live fetus documented on ultrasound examination between 15 and 22 weeks. Only singleton gestations were included. Logistic regression analysis was used to adjust for potential confounders between the groups. RESULTS: Among 58,436 women meeting the inclusion criteria, complete outcome data were available for 51,557 (88%), 11,746 (91%) in the amniocentesis group and 39,811 (87%) in the group that did not have amniocentesis. The fetal loss (miscarriages and intrauterine fetal death) rate in the amniocentesis group was 0.4% compared with 0.26% in those without amniocentesis (relative risk 1.6, 95% confidence interval [CI] 1.1-2.2). Fetal loss less than 24 weeks (including induction for ruptured membranes and oligohydramnios) occurred in 0.97% of the amniocentesis group and 0.84% of the group with no procedure (P=.33). The fetal loss rate less than 24 weeks attributable to amniocentesis was 0.13% (95% CI -0.07 to 0.20%) or 1 in 769. The only subgroup that had a significantly higher amniocentesis attributable fetal loss rate was women with a normal serum screen (0.17%, P=.03). CONCLUSION: The institutional fetal loss rate attributable to amniocentesis is 0.13%, or 1 in 769 at Washington University School of Medicine. The total fetal loss rate was not significantly different from that observed in patients who had no procedure.