<p>The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism influences renin-angiotensin-aldosterone system activity and may modulate cardiovascular adaptations to exercise. Yet, evidence regarding genotype-dependent responses to aquatic high-intensity interval training (HIIT) in postmenopausal women is limited. We aimed to compare the effects of 12-week aquatic HIIT on blood pressure, lipid profile, and arterial stiffness between postmenopausal women with the ACE II genotype and those carrying at least one D allele (ID/DD genotype). Sixty postmenopausal women aged 45–75 years were recruited, with ten participants voluntarily withdrawing from the study and three lost to follow-up. A total of 47 participants completed the intervention (21.7% attrition). Participants were stratified into ACE II (n = 25, 59.0 ± 5.52 years) and ID/DD (n = 22, 57.4 ± 7.52 years) genotype groups. Participants performed a 12-week aquatic HIIT program, with three 40-minute sessions per week. Each session consisted of a 6-minute warm-up, 30&#xa0;min of main training (involving strength and jumping exercises), and a 4-minute cool-down. key cardiovascular outcomes were measured at pre- and post-intervention. Following a 12-week aquatic HIIT program, no significant differences were observed in post-intervention systolic blood pressure (SBP), diastolic blood pressure (DBP), or mean arterial pressure (MAP) between the II and ID/DD groups (all p &gt; 0.05). While no significant between-group differences were found in brachial-ankle pulse wave velocity (baPWV) on either side (p = 0.058, 0.086), a greater magnitude of change in baPWV values was observed in the ID/DD group. Within-group analyses revealed that the II group exhibited significant reductions in SBP, DBP, MAP, and baPWV(right) (p = 0.023, 0.041, 0.020, 0.019), whereas the ID/DD group showed significant increases in baPWV (right/left, p = 0.013, 0.002). Post-intervention TG levels were significantly lower in the ID/DD group compared to the II group (p = 0.000), with a non-significant trend toward higher HDL-C levels (p = 0.053). Both groups demonstrated significant improvements in lipid profiles, characterized by increased HDL-C and decreased LDL-C (p &lt; 0.05). The aquatic HIIT program significantly improved blood lipids in postmenopausal women, yet no significant ACE genotype-specific effects were observed on blood pressure or arterial stiffness. While the II group exhibited favorable reductions in blood pressure, the ID/DD group showed increased arterial stiffness, suggesting potential vascular risks and underscoring the need for monitoring during exercise.</p><p><?noindent??><i>Trial registration</i>: ChiCTR2400087544 (July 30, 2024). </p>