Epigenomics is the study of modifications to the genetic material without changes to the DNA sequence, one such modification is methylation of nucleotides. DNA methylation is associated with gene regulation and is studied in a variety of fields such as cancer and ageing. Quality control is essential when designing research studies to ensure that the end result is not affected by poor quality data. In this study, the aim was to define robust quality parameters for whole methylome sequencing for Illumina next generation sequencing data. Three different library preparation protocols, all designed for methylation analysis, has been compared: Accel-NGS Methyl-Seq DNA library, NEB Next Enzymatic Methyl-seq and SPlinted Ligation Adapter Tagging. All samples were sequenced on the Illumina NovaSeq 6000 with paired-end 150 bp. An evaluation of alignment software was also included in the study. The nf-core methylseq pipeline version 1.6.1 was used to process all samples in the study. The pipeline was run multiple times with different settings depending on library type and software choice. Throughout the study, the parameters puc19, lambda and alignment rate showed consistency whereas overall methylation rate and coverage were affected by origin of sample material and study design. In conclusion, not all proposed quality parameters were suitable for general quality control since study design and origin of sample material have impact, but alignment rate and the controls puc19 and lambda shows great promise for general quality control. Future work to establish sample material specific thresholds for methylation rate is encouraged.