Objective: The rapid increase of cell-free fetal DNA analysis for Down syndrome screening requires evidence-based clinical practice guidelines for noninvasive prenatal testing (NIPT). Several studies show that the quality of many guidelines is low and there are still many health areas where this quality is not systematically evaluated. Given the absence of research, in the NIPT field, we used an internationally validated tool to evaluate a set of three NIPT practice guidelines and to look at dimensions that can be improved.Methods: Four appraisers, experts in prenatal screening, evaluated three main NIPT guidelines published in the last 2 years using the AGREE II (Appraisal of Guidelines for Research and Evaluation II), a tool specifically designed for guideline quality appraisal.Results: Guidelines scored higher in domains related with scope, purpose, and clarity of presentation, and lower in stakeholder involvement and rigor of development. Intradomain items evaluation showed asymmetries between guidelines. The UK-NSC was the guideline with the best scores.Discussion: Several areas of NIPT guidelines, such as stakeholders involvement, selection of supporting evidence, external reviews, updating processes, and competing interests disclosure, can be improved. Appraisers recommend modifications to all NIPT guidelines that can lead to substantial improvements in their methodological quality and subsequently make a contribution to prenatal screening improvement.