Cell-free DNA (cfDNA) serves as a valuable biomarker for early disease detection and monitoring. However, the use of cfDNA for analysis faces challenges owing to general low but variable abundance and fragmentation. Preanalytical factors, including cfDNA extraction, impact cfDNA quality and quantity. Efficient and robust cfDNA extraction is essential for reliable results in downstream applications, and various commercial extraction methods exist, each with trade-offs. To aid researchers and clinicians in choosing the proper cfDNA extraction method, manual, semiautomated, and automated methods were evaluated, including the QIAamp Circulating Nucleic Acid Kit (manual and QIAcube), QIAamp MinElute ccfDNA Kit (QIAcube), and QIAsymphony DSP Circulating DNA Kit (QIAsymphony).