This study compared the metabolic responses of 13 endurance runners, familiar with nonweight-bearing water immersion (WI) running, at ventilatory threshold (Tvent) and maximal effort (VO2max) for both treadmill and WI running performance. Oxygen consumption (VO2), ventilation (VE), heart-rate (HR), VE/VO2, respiratory exchange ratio (RER), perceived exertion (RPE), and stride frequency (SF) were measured at Tvent and VO2max. Paired t-tests revealed higher VO2max (59.7 vs 54.6 ml.kg.-1min-1), HRmax (190 vs 175 bpm), RERmax (1.20 vs 1.10), VO2 at Tvent (46.3 vs 42.8 ml.kg.-1min-1), HR at Tvent (165 vs 152 bpm) for treadmill versus WI running, respectively. Treadmill and WI VEmax (109.0 vs 105.8 l.min-1), RPEmax (20), VE at Tvent (66.4 vs 65.7 l.min-1), RER at Tvent (0.99 vs 0.98), RPE at Tvent (13 vs 12) were similar, as were blood lactate [BLa] values obtained at 30 s (10.4 vs 9.8 mmol.l-1) and 5 min (9.7 vs 9.2 mmol.l-1) post-test. SF values over time were higher on the treadmill. The lower WI VO2max with similar peak [BLa] and lower SF values suggests that the active musculature and muscle recruitment patterns differ in WI running due to the high viscosity friction of water, and the nonweight-bearing nature of WI running.