Purpose: Orthostatic hypotension, leading to cerebral hypoperfusion, can result in postural instability and falls in older adults. We determined the efficacy of a novel, intermittent pneumatic compression system, applying pressure around the lower legs, as a countermeasure against orthostatic stress in older adults. Methods: Data were collected from 13 adults (4 male) over 65 years of age. Non-invasive ultrasound measured middle cerebral artery blood velocity (MCAv) and finger photoplethysmography measured mean arterial blood pressure (MAP). Intermittent lower leg compression was applied in a peristaltic manner in the local diastolic phase of each cardiac cycle to optimize venous return during 1-min of seated rest and during a sit-to-stand transition to 1-min of quiet standing with compression initiated 15 s before transition. Results: During seated rest, compression resulted in a 4.5 ± 6.5 mmHg increase in MAP, and 2.3 ± 2.1 cm/s increase in MCAv (p < 0.05). MAP and MCAv increased during the 15 s of applied compression before the posture transition (2.3 ± 7.2 mmHg and 2.1 ± 4.0 cm/s, respectively, p < 0.05) with main effects for both variables confirming continued benefit during the transition and quiet stand periods. Conclusions: Application of carefully timed, intermittent compression to the lower legs of older adults increased MAP and MCAv during seated rest and maintained an elevated MAP and MCAv during a transition to standing posture. Future research could assess the benefits of this technology for persons at risk for orthostatic hypotension on standing and while walking in an effort to reduce injurious, unexplained falls in older adults.