OBJECTIVES: We intended to assess the cost-effectiveness of adding unconjugated oestriol (uE3) in maternal serum screening for Down's syndrome in Taiwan, where there is a decreasing birth rate but an increasing trend of old women having pregnancies. METHODS: We used logistic regressions to estimate the risk of Down's syndrome with maternal age and different combinations of biomarkers. Cost-effectiveness analysis was presented in terms of the average and incremental cost-effectiveness ratios. Sensitivity analyses with different parameters were performed. RESULTS: Given a cut-off point of 1:270 for the confirmation of Down's syndrome with amniocentesis, the average cost per case averted for maternal age above 35 years only, double test [alpha-fetoprotein (AFP) and human chorionic gonadotrophin (hCG)] and triple test (AFP, hCG and uE3) were estimated as $14,561, $42,367 and $37,424. The additional costs per case averted for double test and triple test (compared with maternal age above 35 years) were $135,950 and $77,394, respectively. The additional cost per case averted for triple test was $15 199 compared with double test. CONCLUSIONS: The performance of triple test is not only more effective in detecting Down's syndrome cases but also more cost-effective than double test in this study. [ABSTRACT FROM AUTHOR]