Background: Blood flow restriction exercise (BFR-E) could be a useful training adjunct for patients with weakness after stroke to augment the effects of exercise on muscle activity. We aimed to examine neurophysiological changes (primary aim) and assess patient perceptions (secondary aim) following BFR-E. Methods: Fourteen participants with stroke performed BFR-E (1 session) and exercise without blood flow restrictsion (Exercise only) (1 session), on two days, \approx7 days apart. In each session, two sets of tibialis anterior (TA) contractions were performed and electromyography (EMG) was recorded. Eight participants underwent transcranial magnetic stimulation (single-pulse stimulation, short interval intracortical inhibition (SICI), intracortical facilitation (ICF)) and peripheral electrical stimulation (maximal peak-to-peak M-wave (M-max)) of the TA before, immediately-after, 10-min-after and 20-min-after BFR-E and Exercise only. Numerical rating scores (NRS) for pain, discomfort, fatigue, safety, focus and difficulty were collected for all subjects (n = 14). Paired comparisons and linear mixed models assessed the effects of BFR-E and Exercise only. Results: No adverse events due to exercise were reported. There was no contraction-number \times condition interaction for EMG amplitude during exercise (p = 0.15), or time \times condition interaction for single-pulse stmulation, SICI, ICF or M-max amplitude (p = 0.34 to p = 0.97). There was no difference between BFR-E and Exercise only in NRS scores (p = 0.10 to p = 0.50). Conclusion: Using our training paradigm, neurophysiological parameters, feasibility, tolerability and perceptions of safety were not different between BFR-E and Exercise only. As participants were generally well-functioning, our results are not generalizable to lower functioning people with stroke, different (more intense) exercise protocols or longer term training over weeks or months.