PURPOSE: Iron deficiency is prevalent in distance runners and may impair endurance performance. The current practice of oral supplementation is slow and often not well tolerated. The aim of this study was to assess the efficacy of intravenous (IV) iron supplementation (ferric carboxymaltose) compared with oral supplementation (ferrous sulfate) on iron status, hemoglobin mass (Hb mass), and physiological indices of running performance in distance runners. METHODS: Twenty-seven highly trained distance runners with low (LOW) (ferritin <35 μg·L -1 and transferrin saturation <20%, or ferritin <15 μg·L -1) or suboptimal (SUB) iron status (ferritin <65 μg·L -1) were supplemented with either IV iron (Ferinject®) or oral (ORAL) supplements (Ferrogradumet) for 6 wk. Iron status and Hb mass were assessed before supplementation and at 1, 2, 4, 6, and 8 wk in the four groups (IV LOW, IV SUB, ORAL LOW, and ORAL SUB). In addition, athletes completed a treadmill running test for running economy, lactate threshold, and VO 2max before and after supplementation. RESULTS: Both forms of supplementation substantially increased ferritin levels in all four groups. IV supplementation resulted in higher ferritin in both IV groups compared with both ORAL groups from week 1 onward. Hemoglobin concentration did not change substantially in any group. Hb mass increased in IV LOW (mean = +4.9%, 90% confidence interval [CI] = 1.1%-8.9%) and was accompanied by an increase in VO 2max (mean = +3.3%, 90% CI = 0.4%-6.3%) and run time to exhaustion (mean = +9.3%, 90% CI = 0.9%-18.3%. CONCLUSIONS: IV supplementation can effectively increase iron stores in iron-deficient runners within 6 wk and, if Hb mass is compromised, may enhance endurance capacity by facilitating erythropoiesis. Hb mass appears a more sensitive tool for measuring changes in whole body hemoglobin than hemoglobin concentration and may be useful in the diagnosis and follow-up for iron deficiency.