Prenatal testing is vital for the timely diagnosis of serious health issues of the fetus during pregnancy. Non-invasive prenatal testing (NIPT) is a highly effective and innovative method that entails minimum risk for the mother and the fetus, but incurs high economic cost. The present study aims to systematically review international research and identify whether reimbursement of NIPT by healthcare systems would be cost-effective. In a 2-month period (January-February 2019), a systematic review of the literature on the economics evaluation of NIPT was conducted using the databases PubMed, Cochrane and Google Scholar. PICO methodology was applied in order to design the research question, while the search included randomized and non-randomized clinical trials and other systematic reviews. Specific search terms and inclusion-exclusion criteria were pre-defined. No language restrictions have been included. The analysis was performed through qualitative methodological approach and the Quality for Health Economic Studies (QHES) tool was utilized to identify bias. The search procedure identified 434 studies, which were reduced to 393 after removal of duplicate findings. Upon review of abstracts and full texts, the final search resulted in 16 studies. Based on the analysis, NIPT is considered clinically the most effective test compared to other methods (14/16 studies) and it entails the highest cost among those methods investigated in the studies. Also, its high cost is an important obstacle towards its universal reimbursement by healthcare systems, as from the third-party payer perspective it is not considered cost-effective, while it is considered cost-efficient from the societal perspective. NIPT is characterized by the highest clinical effectiveness, specificity and sensitivity in identifying chromosome abnormalities compared to a variety of other methods of prenatal testing, although its high cost prevents it from being reimbursed by healthcare systems. Further economic evaluation research could provide sufficient documentation on its overall value in the field.