The objective of this study was to investigate the effects of wearing compression socks (CS) on performance indicators and physiological responses during prolonged trail running. Eleven trained runners completed a 15.6 km trail run at a competition intensity whilst wearing or not wearing CS. Counter movement jump, maximal voluntary contraction and the oxygenation profile of vastus lateralis muscle using near-infrared spectroscopy (NIRS) method were measured before and following exercise. Run time, heart rate (HR), blood lactate concentration and ratings of perceived exertion were evaluated during the CS and non-CS sessions. No significant difference in any dependent variables was observed during the run sessions. Run times were 5681.1±503.5 and 5696.7±530.7 s for the non-CS and CS conditions, respectively. The relative intensity during CS and non-CS runs corresponded to a range of 90.5-91.5% HRmax. Although NIRS measurements such as muscle oxygen uptake and muscle blood flow significantly increased following exercise (+57.7% and + 42.6%,+59.2% and + 32.4%, respectively for the CS and non-CS sessions, P<0.05), there was no difference between the run conditions. The findings suggest that competitive runners do not gain any practical or physiological benefits from wearing CS during prolonged off-road running. © 2012 © 2012 European College of Sport Science.