The aim of the present study was to investigate whether methylation of the angiotensin I converting enzyme 2 (ACE2) promoter increases the risk of essential hypertension (EH). A total of 96 patients with EH were recruited and 96 sex‑ and age‑matched healthy controls. Methylation of 5 CpG dinucleotides in the ACE2 promoter was quantified using bisulfite pyrosequencing. Logistic regression and multiple linear regression were used to adjust for confounding factors and the generalized multifactor dimensionality reduction (GMDR) method was applied to investigate high‑order interactions. Methylation of CpG4 (adjusted P=0.020) and CpG5 (adjusted P=0.036) was significantly higher in patients with EH, with frequency 97.56±5.65% and 12.75±4.15% in EH individuals and 95.73±9.11% and 11.47±3.67% in healthy controls. GMDR detected significant interaction among the 5 CpG sites (odds ratio=7.33, adjusted P=0.01). Furthermore, receiver operating characteristic curves identified that CpG5 methylation was a significant predictor of EH. Notably, CpG2 methylation was significantly higher in males than in females (adjusted P=0.018). Conversely, CpG5 methylation was significantly lower in males (adjusted P=0.032). These results indicated that aberrant methylation of the ACE2 promoter may be associated with EH risk. In addition, sex may significantly influence ACE2 methylation.