Ischemic preconditioning (IP) protects both the tissue where it is applied (Local IP) and others (Remote IP) against injury induced by prolonged ischemia. Local IP can increase maximal power output in an exercise test. However, it is not clear whether Remote IP could also increase physical performance and which mechanisms associates IP and physical performance. This study investigated the effects of Remote IP on physical performance during handgrip exercise and possible mechanisms associated. Thirteen men underwent randomly Remote IP or Sham intervention in 2 sessions. After that, they performed handgrip exercise until task failure. Time to task failure was measured as well as brachial blood flow and conductance, forearm normalized concentration of deoxygenated hemoglobin and myoglobin (Deoxy-Hb norm.), tissue oxigenation index (TOI norm.), heart rate (HR), stroke volume (SV), mean arterial pressure (MAP) and total peripheral resistance (TPR). Comparisons between conditions were made at equal exercise time (20%, 40%, 60%, 80% and 100% of shorter session exercise time) and at peak exercise of each session. Measurements of maximal voluntary contraction, exercise time and brachial artery diameter were reproducible (intraclass correlation coefficient >0.9) and mean coefficient of variation was between 5.1% to 13.5%. Time to task failure increased by 25.3%, from 191±21 s after Sham intervention to 244±37 s after Remote IP (Student’s T test P=0,019). The increment of exercise time between Remote IP and Sham correlated positively to the increment of blood flow, conductance, TOI norm. and SV at 100% of total exercise time, and correlated negatively to the impairment of Deoxy-Hb norm., HR, MAP and TPR at 100% of total exercise time. At peak exercise, Remote IP led to a higher Deoxy-Hb norm. and lower TOI norm. Subjects who were responders to Remote IP (exercise time increment >13.5%; n=6) had lower MAP and TPR and higher VS at 100%, compared to Sham. At peak exercise, Remote IP increased blood flow. However, Deoxy-Hb norm. and TOI norm. were similar between conditions in these subjects. In conclusion, Remote IP increased exercise performance, possibly by improvement of blood flow and vascular conductance response to exercise. This improvement, in turn, could be due to a greater local vasodilation and an attenuation of sympathetic tone.