Objective: This study aimed to compare endothelial microcirculatory function in hypertensive and diabetic (HD) and healthy postmenopausal women before and after nasal application of 17A-estradiol. Methods: Seventy-one women aged 42 to 59 years within 10 years of menopause, divided into HD (n = 31) and similar-age healthy (n = 40) women were evaluated noninvasively through nailfold videocapillaroscopy before and 1 hour after estradiol, measuring basal (RBCV) and maximum (RBCVmax) red blood cell velocity after 1 minute of arterial occlusion, representing baseline and endothelial-mediated vasodilation, and time to reach RBCVmax (TRBCVmax), representing microvascular compliance/stiffness. Results: Hot flashes did not differ from or affect microvascular results. Before estradiol, HD showed lower RBCV (1.495 +/- 0.20 vs 1.52 +/- 0.10 mm/s, P = 0.019), borderline lower RBCVmax (1.655 +/- 0.09 vs 1.706 +/- 0.10 mm/s, P = 0.054), and shorter TRBCVmax (7.94 +/- 1.44 vs 8.8 +/- 2.03 s, P = 0.011) compared with healthy women. After estradiol, RBCV and RBCVmax increased, and TRBCVmax decreased in both groups (P = 0.0001 for all). HD women showed a higher RBCV increment (14.6% +/- 2% vs 11.1 +/- 1.4%, P = 0.021) associated with a smaller TRBCVmax reduction (23.6% +/- 2% vs 31% +/- 2%, P = 0.045). Changes in RBCVmax did not differ between HD (11.6% +/- 1%) and healthy (8.3% +/- 1.3%, P = 0.1) women. RBCV, RBCVmax, and TRBCVmax absolute values after estradiol were similar between groups. Past oral contraceptive exposure (P = 0.035) and cigarette smoking (P = 0.047) influenced healthy women's microvascular responses to estradiol, whereas triglyceride levels impaired HD vasodilation (P = 0.028). Conclusions: Before estradiol, HD presented impaired microvascular dilation and compliance compared with control women of similar age. After estradiol, HD recovered microvascular endothelial-mediated dilation, reaching similar absolute values, but the smaller reduction in TRBCVmax suggests irreversible microvascular stiffness.