Objective <p>This study aimed to investigate the relationship between ACE2 expression in peripheral blood and the prognosis of patients with adrenal adenoma and hypertension.</p> Methods <p>We recruited 80 patients with adrenal adenoma and hypertension (47 males, 33 females) treated between March 2021 and September 2022. Patients were divided into high ACE2 expression (<i>n</i> = 26) and low ACE2 expression (<i>n</i> = 54) groups. General patient data, blood pressure, serum potassium, creatinine, and hormone levels (cortisol, aldosterone, catecholamines) were compared. The frequency of hypertensive episodes with palpitations was recorded. Correlations between ACE2 expression and prognosis were analyzed using Pearson correlation and Cox regression models.</p> Results <p>The ACE2 high expression group had significantly lower blood pressure, serum creatinine, and hormone levels (<i>P</i> &lt; 0.001), but higher serum potassium (<i>P</i> &lt; 0.001) compared to the low expression group. Over 3 months, the incidence of hypertensive episodes with palpitations was lower in the high expression group (7.69%) compared to the low expression group (24.07%) (<i>P</i> = 0.002). The frequency of episodes was also lower in the high expression group (<i>P</i> = 0.016). Pearson correlation analysis showed a negative correlation between ACE2 expression and poor prognosis (<i>P</i> &lt; 0.001). Multivariate Cox regression confirmed low ACE2 expression as an independent risk factor for poor prognosis (<i>P</i> &lt; 0.001).</p> Conclusion <p>High ACE2 expression is associated with improved cardiovascular and renal function and lower incidence of hypertensive episodes in patients with adrenal adenoma and hypertension, suggesting a protective role of ACE2 in mitigating hypertension-related complications.</p> Clinical trial number <p>Not applicable.</p>