Although acclimatization to moderate altitude (MA) is thought to be unnecessary or to require minimal adaptation, retrospective data from the U.S. Air Force Academy (USAFA), a military college located at 2210 m, suggested otherwise. To further examine the utility of USAFA as a model for MA acclimatization, a longitudinal experimental design was prospectively utilized to determine the magnitude and time course of selected hematological and performance parameters following 46 weeks at this unique MA setting. Incoming USAFA male freshmen (n=55) were divided into experimental groups based on prior residence at sea level (SL) or MA. Hematological and performance parameters were repeatedly assessed during their entire first year at MA. Hematological data consisted of a complete blood count (CBC) with reticulocyte parameters, as well as determination of serum levels of ferritin, erythropoietin, and soluble transferrin receptor (sTfR). Performance testing included aerobic (1.5-mile run) and physical (push-ups, sit-ups, pull-ups, and standing long jump) fitness tests, maximal aerobic capacity, and running economy. Significant (p<0.05; main effect) hematological differences between SL and MA subjects were observed for the majority of the study. MA subjects had a significantly higher hemoglobin concentration ([Hb], +5.5%), hematocrit (+2.8%), and serum ferritin (+59.0%) and significantly lower sTfR (-11.4%) values than their SL peers. Although both serum ferritin and sTfR demonstrated a significant altitude group x time interaction, [Hb] and hematocrit did not. A significant main effect of altitude without interaction was also observed for performance parameters, with SL subjects having a significantly lower Vo2peak (-5.9%), slower 1.5- mile run time (+5.4%), poorer running economy (+6.6%), and lower composite physical fitness test score (-13.9%) than MA subjects. These results suggest that complete acclimatization to 2210 m by former SL residents may require lengthy physiological adaptations, as both hematological and physical performance differences persisted between groups. Further research at this uniquely well controlled MA setting is warranted.