These protocols describe two methods to extract high molecular weight genomic DNA from a human cell line. We recommend QIAGEN Puregene Cell Kit and the QIAGEN Genomic-tip 500/G. Both methods produced high sequencing output and long read lengths, although the read lengths produced by the Puregene Kit were slightly longer than those produced by the Genomic-tip. We also recommend the use of SPRI size selection prior to sequencing. The sequencing performance was assessed using the Ligation Sequencing Kit.