OBJECTIVE: To estimate the fetal loss rate in our center and evaluate the risk factors associated with such losses after chorionic villus sampling (CVS). METHODS: This is a retrospective cohort study including all women undergoing chorionic villus sampling and a control group that had no invasive procedure at a single center over a 16-year period. Fetal loss was defined as any loss before 24 weeks of gestation. Univariable and multiple logistic regression analyses were used to compare pregnancies resulting in fetal loss to those without a loss and to adjust for potential confounders between the groups. RESULTS: Of 5,243 women who had CVS who were compared with 4,917 women seen before 14 weeks who had no invasive procedure, there were 138 (2.7%) fetal losses before 24 weeks of gestation in the CVS group compared with 161 (3.3%) in the control group (relative risk 0.80, 95% confidence interval, 0.64-1.0). The difference in loss rate of -0.7% (95% confidence interval, -0.02 to 1.3) between the CVS group and those who had no procedure was not statistically significant at P<.05. The significant risk factors for fetal loss were African-American maternal race, at least two aspirations/needle insertions, heavy bleeding during CVS, maternal age younger than 25 years, and gestational age at performing CVS before 10 weeks. CONCLUSION: The estimated fetal loss rate after CVS was not significantly different from the group that had no procedure. Significant predictors of fetal loss after CVS were identified, but the accuracy of the final model for predicting fetal loss was only modest.