The aim of this paper was to conduct a systematic review of the cost-effectiveness of the analysis of cell-free DNA in maternal blood, often called the non-invasive prenatal test (NIPT), in the prenatal screening of trisomy in chromosomes 21, 18 and 13. MEDLINE, MEDLINE in process, EMBASE, and Cochrane Library were searched in April 2017. We selected: (1) economic evaluations that estimated the costs and detected cases of trisomy 21, 18 or 13; (2) comparisons of prenatal screening with NIPT (universal or contingent strategies) and the usual screening without NIPT, (3) in pregnant women with any risk of foetal anomalies. Studies were reviewed by two researchers. Data were extracted, the methodological quality was assessed and a narrative synthesis was prepared. In total, 12 studies were included, four of them performed in Europe. Three studies evaluated NIPT as a contingent test, three studies evaluated a universal NIPT, and six studies evaluated both. The results are heterogeneous, especially for the contingent NIPT where the results range from NIPT being dominant to a dominated strategy. Universal NIPT was found to be more effective but also costlier than the usual screening, with very high incremental cost-effectiveness ratios. One advantage of screening with NIPT is lower invasive procedure-related foetal losses than with usual screening. In conclusion, the cost-effectiveness of contingent NIPT is uncertain according to several studies, while the universal NIPT is not cost-effective currently.