Our goal in writing this guideline article was to summarize the rapid advancements in SDF measurement and propose specific clinical indications in an evidence-based approach. Subsequently, the literature on SDF testing, including etiologies, risk factors, laboratory assays, implications on reproductive outcomes and appropriate clinical management has expanded dramatically. Nevertheless, the clinical application of SDF testing in male factor evaluation continues to be debated, lacks consensus and is underutilized. We therefore believe there is an urgent need of a high-quality evidence-based review and clinical guideline to consolidate the clinical role of SDF testing in male infertility evaluation. An expert panel of 24 leading andrologists (includes 14 well known, practicing clinicians with expertise in male infertility and ten renowned researchers in male reproduction and infertility) experienced in SDF have actively collaborated over the past six months to co-author an evidence based clinical guidelines manuscript. The hall mark of our most unique article is that: 1) we have carefully curated all available high quality evidence on the role of sperm DNA fragmentation in clinical management of couples with male factor infertility, 2) developed a consensus on the clinical use of SDF testing in specific scenarios by our team of renowned experts, 3) conducted a SWOT analysis to test the utility of SDF test and lastly 4) our group have conceived and created five original, high quality illustrations to explain the origin, etiologies, risk factors, and the nature of SDF and last, 5) we have created four comprehensive tables covering data from hundreds of studies in support of a) SDF cut off values for the prediction of pregnancy outcomes using different laboratory assays, b) clinical indications for SDF testing with quality of evidence extracted from about 160 clinical trials, c) therapeutic interventions for SDF with quality of evidence extracted from about 70 clinical trials, and last d) comparison of different SDF tests in terms of principles, advantages and disadvantages. This clinical guideline starts with a summary of basic scientific findings on origins, etiologies, risk factors, and the nature of SDF before moving onto the discussion of the available SDF assays. It is followed by clinical indications for the test, supported by various case scenarios. Moreover, recent developments in the clinical management of high SDF are also discussed. Finally, the clinical guidelines are concluded by expert recommendations and Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of SDF in specific male infertility scenarios. This clinicians’ guideline helps the readers reach a better understanding of SDF testing and promote its wider clinical application, which in turn will enhance the reproductive outcome of couples suffering from the debilitating disease of infertility”