Sample preparation is a critical factor for whole genome sequencing (WGS) projects that impacts sequencing yield, read length, and ultimately performance for variant calling and genome assembly. Best practices to optimize performance for PacBio HiFi sequencing are to collect whole human blood, store with potassium EDTA as the anticoagulant for fewer than 2 days at 4°C, and extract DNA from 200 μL of blood using the Nanobind CBB Big DNA kit. When it is not possible to extract from fresh samples, storing samples at 4°C maximizes extraction yield and minimizes degradation for at least 9 days.