OBJECTIVE: To estimate the risk of fetal loss in obese women undergoing amniocentesis and chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study of all women undergoing amniocentesis or CVS. The primary outcome was any fetal loss before 24 weeks of gestation. A secondary analysis was performed examining pregnancy loss within 14 days of the procedure, excluding termination of pregnancy. Obese (body mass index [BMI] 30.0 or higher) and nonobese (BMI lower than 30.0) patients were compared, and the postprocedure loss rate was also estimated by BMI strata. Obese and nonobese patients were compared with univariable and bivariate statistics; multivariable logistic regression models were developed to estimate the effect of maternal obesity. RESULTS: Between obese (n=2,742) and nonobese (n=8,037) women undergoing amniocentesis, no difference existed in the risk of fetal loss before 24 weeks of gestation (4.7% [combined background and procedure loss] compared with 4.2%, adjusted odds ratio [OR] 1.1, 95% confidence interval [CI] 0.8-1.5). For women undergoing CVS, no difference in the risk of pregnancy loss was seen between obese (n=855) and nonobese (n=4,125) women (6.4% compared with 6.3%, adjusted OR 1.0, 95% CI 0.7-1.3). Compared with women not undergoing a procedure, the attributable risk for obese women was 0.3% (95% CI -0.2 to 0.9) amniocentesis and 0.1% (95% CI -0.1 to 0.2) CVS. The difference in fetal loss between the BMI 40.0 or higher and BMI lower than 25.0 groups after amniocentesis was significant after adjusting for maternal age (adjusted OR 2.2, 95% CI 1.2-3.9). This study had greater than 90% power to detect a 50% increase in the risk of pregnancy loss after amniocentesis and CVS (with an α error of 0.05). CONCLUSION: A BMI of 30.0-40.0 does not increase the risk for fetal loss after invasive prenatal diagnostic procedures. A higher loss rates with class III obesity (BMI 40.0 or higher) was observed for amniocentesis procedures. LEVEL OF EVIDENCE: II.