Ancient DNA (aDNA) analyses necessitate the destructive sampling of archaeological material.Currently the dense inner portion of the petrous pyramid, the location of the skull that houses the inner ear, is the most sought after skeletal element for molecular analyses of ancient humans as it has been shown to yield high amounts of endogenous DNA. Destructive sampling of the petrous pyramid, assuming its recovery, is often not recommended for highly valued specimens. To investigate alternatives, we present a survey of human aDNA preservation for each of ten skeletal elements in a skeletal collection from Medieval Germany. Through comparison of human DNA content and quality we confirm best performance of the petrous pyramid and identify seven additional sampling locations across four skeletal elements that yield adequate aDNA for most applications in human palaeogenetics. Our study provides a better perspective on DNA preservation across the human skeleton and takes a further step toward the more responsible use of ancient materials in human aDNA studies. 2 26 27 28 29 30 31 32 33 34 35 36 37 38Recent advances in minimally invasive sampling techniques 26 have led to a better balance between preservation of the anthropological record and the need for the production of reliable genetic data 27,28 ; however, the threat of damage to internal microstructures that form an important basis of morphological assessments 29-31 can still introduce hesitancy on the part of curators and physical anthropologists in making the petrous pyramid available for aDNA applications. These factors, in conjunction with the chance of incomplete recovery of crania at excavation 32 or restricted sampling of highly valued specimens, make the identification of alternative sampling locations based on quantitative evaluations of DNA preservation across the skeleton of clear benefit. Teeth have been widely used for the study of aDNA 33,34 , though the 30-fold covered genome of an archaic hominin from Denisova Cave from a distal phalanx demonstrates molecular preservation in elements that are not typically considered for paleogenetics work 4 . Despite these successes, a systematic and extensive study of differential DNA preservation across multiple human skeletal elements, such as those done in the context of modern forensics 35,36 , has yet to be attempted on archaeological remains. Our limited understanding of DNA preservation across the human skeleton is a significant hurdle for the efficient, practical, and ethical study of aDNA, which has particular relevance to the field of ancient population genetics where large sample sizes are needed for robust analytical resolution.DNA preservation can be influenced by many factors including burial practises and treatment of the deceased, geology, as well as environmental and climatic conditions 37 , where the chronological age of a sample is thought to play only a secondary role 38,39 . To serve as a baseline for future investigations seeking to incorporate and extrapolate the effects of these sources of v...