The aim of this study was to assess the effectiveness of first-trimester screening using a combination of maternal age, nuchal translucency thickness (NT) and maternal serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels for aneuploidy in a Brazilian population in Rio de Janeiro. This was a retrospective study of 546 women who underwent combined screening for aneuploidy between 11 + 0 and 13 + 6 weeks of gestation in a fetal medicine unit in Rio de Janeiro (Perinatal Group—Laranjeiras). NT was measured according to the criteria set by the Fetal Medicine Foundation (FMF). Maternal serum free β-hCG and PAPP-A levels were measured, and the risk of aneuploidy was calculated using The FMF's algorithm. Fetal karyotyping was advised when the risk was 1: 100 or above. All subjects were followed up for pregnancy and fetal outcome. Among the 546 women who underwent the screening program, 37% were 35 years old or above. 15 fetuses (2,7%) were screen positive; this included 2 cases of trisomy 21 and 1 case of trisomy 18. The sensibility was 75% and the specificity was 98%; the positive predictive value was 21%, and the negative predictive value was 99.5%. Among the 545 screen negative fetuses, there was only one case in which aneuploidy was missed and the infant was live born. First-trimester combined screening for aneuploidy was highly effective in the Brazilian population analyzed in this preliminary study.