Treatment of orthostatic hypotension (OH) with pressor agents can worsen supine hypertension, cause drug interactions, or may be contraindicated in patients with cardiovascular disease. Splanchnic venous compression can improve OH but compliance and efficacy are limited with available garments. We developed an automated inflatable abdominal binder that provides servo-controlled compression (40 mm Hg) only on standing. To compare this device to standard of care with the α-1 agonist midodrine we studied ten autonomic failure patients (5 men, 68±2 yrs) who received placebo, their regular midodrine dose (2.5-10 mg), placebo combined with binder and midodrine combined with binder on separate days, in a randomized, single-blind, crossover study. Systolic blood pressure (SBP) was measured with patients seated and standing before and 1 hr postdrug. Midodrine alone and midodrine with the binder deflated increased seated SBP compared to placebo (29±7 and 25±7 vs. 3±6 mmHg at 1 hr, respectively, Figure A, p<0.01 for midodrine). The deflated binder did not increase seated SBP compared to placebo (6±6 mmHg, P=0.771). On standing, midodrine alone and abdominal compression combined with placebo had a similar improvement in orthostatic tolerance (AUCSBP, 253±36 and 238±42 vs. 27±43 mmHg*min for placebo, Figure B). The combination of binder with midodrine produced a greater pressor effect but the difference did not reach significance (359±97 mmHg*min, P=0.06). In conclusion, the automated inflatable abdominal binder is as effective as midodrine, the standard of care, in the management of OH, without increasing seated BP. Combining both therapies may produce an additive response.