Objectives: The effects of acute physical exercise in patients with resistant hypertension remain largely unexplored compared with hypertensive patients in general. We assessed the short-term effects of acute moderate-intensity (MICE) and high-intensity interval exercise (HIIE) on the clinic (BP) and 24-h ambulatory blood pressure (ABP) of patients with resistant hypertension. Methods: Using a crossover randomized controlled design, 10 participants (56 ± 7 years) with resistant hypertension performed three experimental sessions: MICE, HIIE, and control. MICE consisted of continuous treadmill exercise at an intensity of 3–4 metabolic equivalents of energy (METs) until completing 3 kcal/kg and was energy-matched to HIIE (which included six to eight intervals of 3 min duration at 6–7 METs interspersed with 1.5-min rests at 3 METs). In the control session, participants remained seated for 50 min. Flow-mediated vasodilation, autonomic nervous system balance (heart rate variability), exerkines [interleukin (IL)-6, IL-8, IL-15, vascular endothelial growth factor A, irisin, adiponectin, and angiopoietin] and 71 inflammatory-related proteins were also measured. Results: Compared with baseline, HIIE and MICE reduced clinic SBP immediately (P < 0.001 for both) and 90 min (P = 0.001 and P = 0.041, respectively) postexercise. HIIE and MICE also reduced clinic DBP immediately postexercise (P = 0.003 and P = 0.025). By contrast, no changes were found in the control session. On the other hand, no significant effects were noted for 24 h ABP measures or for the rest of variables. Conclusion: Although in patients with resistant hypertension, acute aerobic exercise induces short-term reductions in clinic BP, this stimulus does not suffice to reduce 24 h ABP or to impact on potential biological mechanisms.