The objective of this study was to compare and evaluate the effectiveness of three protocols of intermittent exposure to simulated altitude (hypobaric hypoxia). This was done in order to determine the shortest protocol in which hematological changes were induced. In addition to having some potential therapeutic applications, these protocols have also been used to pre-acclimation of climbers to altitude, and to improve the performance capacity of athletes. These applications are supported by the available evidence that living in hypoxia while training in normoxia is probably more effective than training and living in hypoxia. Three protocols of different duration (days) and exposure (hours) at a simulated altitude of 4,000-5,500m (462-379 Torr) were compared (Protocol A: 17 days and 60 hours; Protocol B: 9 days and 31 hours; and Protocol C: 21 days and 14 hours). The three experimental procedures showed to effectively elicit a significant increase (p<0.05) in packed cell volume (mean increase = 6.6% to 12.6%), hemoglobin concentration (mean increase = 14.7% to 18.7%), red blood cell counts (mean increase = 7.7% to 13.7%), and reticulocyte count (mean increase = 120% to 180%). We conclude that the three protocols we used for intermittent exposure to hypobaric hypoxia effectively elicited hematological adaptative responses. However, protocol B (9 consecutive days, 3-4 h/d) shows to be the most efficient per day of exposure, in terms of hematological adaptation, followed by protocol C (21 alternate day sessions, 1.5 h/d), most efficient in terms of total time (per hours of exposure). Nevertheless, it may be the time availability of the subjects and/or the facility, which will ultimately determine the model of exposure that is chosen.