Objective/Background: Hematopoietic stem cell transplantation (HSCT) is a treatment for benign and malignant hematological diseases. These aggressive treatments cause reduced levels of physical activity, decreased lung function, and worse quality of life. Alterations in pulmonary function tests before HSCT are associated with the risk of respiratory failure and early mortality. The objective of this study was to evaluate functional capacity and lung function before and after HSCT and identify the predictors of mortality after 2 years. Methods: A prospective cohort study was carried out with individuals with oncohematological diseases. The evaluations were carried out in two moments during hospitalization and at hospital discharge. Follow-up was carried out after 48 months. Assessments were carried out on 34 adults, using spirometry, manovacuometry, 6-Minute Walk Test (6MWT), Handgrip Strength Test, and 30-Second Chair Stand Test (30-s CST). Results: There was a statistically significant reduction for the variables in forced vital capacity, forced expiratory volume predicted in the 1st second, Tiffeneau index, handgrip strength, and distance covered (% predicted) on the 6MWT (p < .05). There was a significant difference in the 30-s CST when individuals were compared according to the type of transplant. We found that a 10% reduction in the values of maximum inspiratory pressure (MIP) can predict an increased risk for mortality. Conclusions: Individuals undergoing HSCT have reduced functional capacity, lung function, and muscle strength during the hospitalization phase. Reduction in the values of MIP increases the risk of nonrelapse mortality.