INTRODUCTION: Individuals with disabilities that use wheelchairs as their primary mode to carry out activities of daily living (ADL), and those affected by spinal cord injury (SCI), have been found to live less-active lives than their able-bodied counterparts, often experiencing physiological changes in the body that can contribute to the development of chronic diseases. Autonomic dysreflexia (AD), marked by a sudden increase in blood pressure (BP) from an unfavorable external stimulus on the lower extremities, is a possible condition that can experienced within this population. Electrical muscular stimulation (EMS) combined with blood flow restriction (BFR) on the lower extremities may lead to hemodynamic adaptations and increases in muscle fiber hypertrophy, improving overall function and quality of life. PURPOSE: The purpose of the study is to compare acute hemodynamic and skeletal muscle responses to EMS with and without the addition of BFR among individuals that primarily use wheelchairs for ADL. METHODS: 10 everyday wheelchair users were recruited from University of Alabama Adapted Athletics program to participate in three conditions. Conditions included sessions of EMS only, BFR only, and combined EMS and BFR on the lower extremities for varying lengths of time. EMS stimulated the quadriceps muscles into extension for 30 seconds at a time with 5 seconds of rest in-between, for a duration of 20 minutes. BFR was inflated at 40% of limb occlusion pressure (LOP) for 8 minutes on and off with 4 minutes of deflation between inflation times. Measurements taken pre- and post-trial included blood lactate (mmol) as well as blood flow measures of the posterior tibial artery and vastus medialis (VM) muscle cross-sectional area (VM CSA) using ultrasonography. BP and heart rate (HR) were measured noninvasively and continuously during each condition as well as analyzed in 5-minute increments. BP was closely monitored for the purpose of safety in observing any possible incidences of AD among participants. Blood lactate, posterior tibial artery blood flow parameters, and VM CSA from pre- to post-trial were statistically analyzed by the use of one- and two-way analysis of variance (ANOVA). HR, systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were analyzed by the use of a two-way ANOVA. Percent change was used to analyze HR, SBP, DBP, and MAP with timepoints from pre- to during the trial (10-15 minutes from start) and pre- to recovery time post-trial (5 minutes following the end) for each condition. RESULTS: Blood lactate increased over time within both the EMS+BFR (1.0 ± 0.1 vs. 1.4 ± 0.1; t= -2.73, p= 0.023) as well as BFR only (0.9 ± 0.2 vs 1.5 ± 0.4; t= -2.94, p= 0.017) conditions. There was a significant decrease in posterior tibial artery distance (0.215 ± 0.00 vs. 0.207 ± 0.00; t=2.47, p= 0.036) and area (0.037 ± 0.000 vs. 0.034 ± 0.000; t=2.67, p= 0.026) over time within the BFR only condition. Across all conditions, changes in HR (expressed as a percentage change from baseline) were lower post- compared to during the trial (mean difference [MD], 95% confidence interval [CI]): -5.3% (-10.4, -0.1), with the greatest differences observed within the EMS+BFR condition: -11.3% (-21.1, -1.5). Similar responses were observed for SBP (-18.4% [-27.1, -9.7]) and DBP (-22.9% [-37.7, -8.0]) in the EMS+BFR condition. There were no significant changes in MAP over time or by condition. CONCLUSIONS: EMS+BFR acutely increased blood lactate over time. The BFR only condition also acutely increased blood lactate as well as decreased posterior tibial artery distance and area over time. Compared to baseline, HR increased during the trial across all conditions, but was significantly lower 5 minutes following the trial in the EMS+BFR condition only. Similar responses were observed for SBP and DBP for the EMS+BFR condition only. There were no observed incidences of AD in any of the conditions, with more favorable cardiovascular responses during and following the EMS+BFR trial. Collectively, our findings support the efficacy and safety of using BFR in combination with EMS with the goal of improving vascular health and function among everyday wheelchair users.