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Purpose: Our primary objective was to characterize clinical and procedural factors affecting sample size in chorionic villus sampling (CVS)., Methods: This retrospective, single-site cohort study included singleton pregnancies undergoing transabdominal (TA) and transcervical (TC) CVS between 2020 and 2023. Prenatal and maternal data were obtained from the electronic medical record. Differences by approach and sample size in relation to demographic and pregnancy characteristics were assessed. Linear regression was used to identify factors associated with yield., Results: Data from 240 CVS procedures were included (n = 91 TC CVS and n = 149 TA CVS). Sample size was significantly larger in TC compared to TA approach (37.1 mg vs 32.4 mg, p = 0.04). In unadjusted models, BMI was associated with a lower sample yield (p = 0.01); use of a TC approach was associated with higher sample size yield (p < 0.01); and lateral placenta was associated with significantly larger samples (p = 0.02). After adjusting for approach and placental location, higher BMI remained associated with smaller sample size (parameter estimate: - 0.47 mg (95% CI: - 0.86, - 0.08); p = 0.03)., Conclusion: CVS remains an important prenatal diagnostic tool in early gestation. We find that higher BMI is associated with a smaller sample yield despite differences in approach and placental location., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: This study was reviewed by our institutional review board and was determined to be exempt (COMIRB 23–1751). Patient consent: Based on our study’s IRB exempt status determination and retrospective nature, patient consent was not obtained., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)