The aim of this study was to determine motor unit firing patterns during ischemic versus non-ischemic sustained submaximal isometric contractions of the tibialis anterior muscle. 10 healthy adults attended two experimental sessions approximately 48 hours apart. Both sessions were identical except that the fatigue task in one was performed with a pressure cuff placed above the knee and inflated to 180 mm Hg. Three 5s maximum voluntary contractions (MVCs) were performed prior to and after the fatigue task. Each participant held a target force of 20% MVC until endurance time (peak-to-peak tremor amplitude exceeded 5% MVC). Single motor unit firing rates (11 non ischemic, 9 ischemic) were recorded with intramuscular fine wire electrodes. Mean interspike intervals over 5s time bins were calculated at every 5% endurance time. The endurance time for the ischemic (3.7 ± 0.58 min) fatigue task was significantly (p<0.001) shorter than the non-ischemic (9.5 ± 0.57 min) task. There was no significant difference in mean motor unit firing rates between the two conditions (p=0.883). Within both tests, there was a significant decline in firing rate (ischemic initial: 12.95 ± 0.71 Hz, minimum: 11.41 ± 0.81 Hz, p=0.023; non-ischemic initial: 13.13 ± 0.87 Hz, minimum: 11.15 ± 0.48 Hz, p=0.012). The time to minimum firing rate was significantly (p<0.001) less in the ischemic (1.29 ± 0.2 min) compared to non-ischemic (3.14 ± 0.23 min) condition. Muscle ischemia significantly reduced endurance time and the time to minimum firing rate. However, there were no differences in average motor unit firing rates between the two conditions across the relative phases of endurance time. / text