Abstract Body: Recent studies have shown an association between blood pressure (BP), particularly pulse pressure (PP), in increasing brain tissue pulsatility. However, these studies were conducted in a phantom model or in healthy normotensive adults. Effects of intensive BP lowering on brain tissue pulsatility in hypertensive patients remain unknown. Accordingly, we performed a randomized clinical trial to compare effects of intensive BP lowering to target 24-h ambulatory BP <120/70 mmHg (n=26) vs. target of <130/80 mmHg in the control arm (n =19) in hypertensive patients aged 55-79 with normal cognitive function. The brain tissue pulsatility was assessed by the total tissue motion over one cardiac cycle, using CINE phase contrast MRI, with the velocity encoded in all three directions. In each cardiac cycle, the velocity of the tissue was measured at 16 time points. Brain tissue pulsatility was assessed at baseline and after 1 year of follow up. We found that 24-h ambulatory systolic BP (SBP) was reduced from 134.3±9.8 to 112.1±7.2 mmHg in the intensive arm and from 138.5±11.3 to 122.4±7.8 mmHg in the control arm (both p<0.01). The magnitude of 24-h SBP reduction from baseline was greater in the intensive arm than control arm (23.6 vs. 13.1 mmHg, p=0.052) while 24-h diastolic BP was reduced similarly in both groups (11.6 vs. 9.6 mmHg, p=0.8). Similarly, PP based on 24-h BP was reduced from 57.5±11.7 to 45.1±12.1 mmHg in the intensive BP arm and from 62.2±10.6 to 55.4±10.5 mmHg in the control arm (both p<0.01). The magnitude of PP reduction appeared greater in the intensive compared to control arm but was not statistically different (12.4 vs. 6.8 mmHg, p=0.08). We found that the overall gray-white matter tissue pulsatility per cardiac cycle remained unchanged after 12 months in the intensive arm (0.98±0.18 mm to 0.95±0.17 mm) while the brain pulsatility tended to increase in the control arm (0.85±0.17 mm to 0.92±0.16 mm, p=0.09 for treatment group, interaction-p=0.04). Similarly, the white matter (WM) tissue motion remained unchanged in the intensive arm (0.91±0.16 mm to 0.88±0.15 mm) while the WM pulsatility tended to increase in the control arm (from 0.77±0.14 mm to 0.84±0.15 mm, p=0.06 for group, interaction p=0.03). In conclusion, our data suggested a novel effect of intensive BP lowering in preventing the rise in brain tissue pulsatility in hypertensive patients, which may have an implication in the prevention of an accelerated brain injury related to hypertension.