Aim: • Evaluate the performance of first trimester combined screening (FTS) for Down's syndrome in singleton South Indian urban population. • Use local data to counsel our women and their families. Materials and methods: A retrospective study of singleton pregnancies who underwent the FTS from January 2013 to December 2015. Nuchal translucency scan and double marker were offered to all pregnant women who booked before 13 weeks 5 days gestational age. Pre- and posttest counseling were provided by consultants in obstetrics. Screen positive for Down's syndrome was taken as a posttest risk cut-off of 1:250 and/or NT >95th centile for gestation. The screen positives were offered a diagnostic test. Screen negatives were counseled about the low risk for Down's syndrome. The outcome of screening, diagnostic testing, and newborn phenotype and genotype were assessed. Results: Among 735 singleton pregnancies screened, 2 Down's syndrome fetuses were identified on diagnostic testing (among 13 screen positives). The detection rate with screening was 100%. There was a 1.5% false screen positive rate in singletons. There were no false-negatives during the study period. Conclusion: The NHS United Kingdom screening program targets a detection rate of 90% for a screen positive rate of 2% using a posttest risk cut-off 1 in 150 or NT >95th centile. First trimester Down's syndrome screening in this study of urban South Asian population had a 1.5% false-positive rate and 0% false-negative rate. The study analysis was based on a posttest risk cut-off of 1 in 250. All true screen positives had a risk cut-off of 1 in 150. Clinical significance: A risk cut-off of 1 in 150 appears to apply to our population when FTS is performed following the standards set by the fetal medicine foundation.