To evaluate the performance of a new first trimester web-based software for the detection of chromosomal anomalies using a combination of ultrasound and biochemistry. Design. Registry-based cohort study. Setting. Ultrasound units in the Stockholm region. Population. 20 710 women with singleton pregnancies were examined at 11+0 to 13+6 weeks' gestational age during a three-year period 2006–2009. Methods. The risks for trisomy 21, 13 and 18 were calculated using a combination of maternal age, serum markers and nuchal translucency. Individual risk estimates were calculated and then reported to a web-based system using a new algorithm based on likelihood ratios of each marker derived from Gaussian distributions in normal and affected pregnancies. Main outcome measures. The impact on rates of invasive testing and the incidence of children born with Down's syndrome after implementing the method. Results. Approximately a third of all pregnant women in the region were examined with the combined test. The detection and test positive rates for Down's syndrome was 90 and 6.8%, respectively. Invasive testing among pregnant women decreased from 15 to 8% after introducing the method but the incidence of children born with Down's syndrome did not decrease during the study period. Conclusion. The new web-based software is an effective method for the detection of trisomy 21 with similar performance compared to other programs. However, it needs to be offered to all pregnant women to have an impact on the incidence of Down's syndrome.