This Application Note describes the use of Covaris Adaptive Focused Acoustics (AFA) technology to extract DNA from FormalinFixed, Paraffin Embedded (FFPE) tissues. When an AFA treatment is applied to a FFPE sample, it simultaneously deparaffinizes the sample, emulsifies the paraffin, and rehydrates the tissue. This is a mechanical process which eliminates the use of hazardous organic solvents. Using currently available methods, DNA extracted from FFPE tissues is not of sufficient quality for the sensitive, reproducible molecular analysis required for clinical research and diagnostics. The Covaris FFPE DNA Purification Kit provides a high yield and high-quality solution for DNA extraction from FFPE tissue samples. Traditional quality control tests, such as DNA fragment size distribution and concentration, are not indicative of the quality required for successful assays. Here, the quality of the extracted DNA with the Covaris FFPE DNA Purification Kit is tested by a multiplex PCR-based quality control assay, showing the DNA is purified with yields more than 3 times higher than other commercially available extraction methods and is more readily available for PCR amplification. Overall, this new FFPE DNA extraction solution greatly enhances DNA availability, improves reproducibility, reduces hands on time, and ensures the seamless integration with Next Generation Sequencing (NGS) and other molecular analysis applications, making it a perfect solution for high value, often irreplaceable, clinical samples.