Background: Prenatal screening tests for trisomy 21 that combine measurement of nuchal translucency in the first trimester of pregnancy with serum marker testing were introduced in France in 2009, following the publication of recommendations by the Haute Autorité de Santé (HAS) in 2007. The objective of this study is to evaluate the impact of the use of these prenatal screening tests on trends in the number of invasive procedures (amniocentesis and chorionic villus sampling) and prenatal diagnoses of chromosomal abnormalities. Method: Annual reports from all prenatal cytogenetics and biochemistry laboratories in France from 2009 to 2012 were analyzed. The frequency of positive test results, invasive procedures, and the predictive value of screening tests, as well as the number of prenatal diagnoses of trisomy 21, were compared over time and by type of screening test. Results: The number of women who underwent a maternal serum marker screening test increased from 673,444 to 684,745 over the study period, representing approximately 85% of all births. The uptake of the first-trimester combined test was very significant, as it accounted for 70% of all tests used in 2012. The frequency of positive test results decreased from 8.8% to 4.1% (p<0.001), accompanied by a 47% reduction in invasive procedures, representing 37,478 fewer procedures. The positive predictive value (PPV) of the tests rose from 1.3% to 4% (p<0.001), due to the high PPV of first-trimester combined tests compared to that of second-trimester tests (5.6% versus 1.9% in 2012, p<0.001). The number of cases of trisomy 21 diagnosed prenatally did not decrease: it rose from 1,918 in 2009 to 1,971 in 2012. Conclusion: The introduction of combined prenatal screening tests for trisomy 21 has led to a very significant reduction in the number of invasive procedures in France, preventing approximately 200 miscarriages without reducing the number of prenatal diagnoses of trisomy 21. The evaluation of screening for trisomy 21 in the general population is ongoing at the French Biomedicine Agency.