Currently, noninvasive prenatal testing (NIPT) is only recommended in high‐risk women following conventional Down syndrome (DS) screening, and it has not yet been included in the Australian DS screening program.

To evaluate the cost‐effectiveness of different strategies of NIPT for DS screening in comparison with current practice.

A decision‐analytic approach modelled a theoretical cohort of 300,000 singleton pregnancies. The strategies compared were the following: current practice, NIPT as a second‐tier investigation, NIPT only in women >35 years, NIPT only in women >40 years and NIPT for all women. The direct costs (low and high estimates) were derived using both health system costs and patient out‐of‐pocket expenses. The number of DS cases detected and procedure‐related losses (PRL) were compared between strategies. The incremental cost per case detected was the primary measure of cost‐effectiveness.

Universal NIPT costs an additional $134,636,832 compared with current practice, but detects 123 more DS cases (at an incremental cost of $1,094,608 per case) and avoids 90 PRL. NIPT for women >40 years was the most cost‐effective strategy, costing an incremental $81,199 per additional DS case detected and avoiding 95 PRL.

The cost of NIPT needs to decrease significantly if it is to replace current practice on a purely cost‐effectiveness basis. However, it may be beneficial to use NIPT as first‐line screening in selected high‐risk patients. Further evaluation is needed to consider the longer‐term costs and benefits of screening.