A quasi-experimental longitudinal design was used to compare pre- and posttraining biomechanical and physiological characteristics of wheelchair propulsion in manual wheelchair users (MWCU) across fresh and fatigue states. An instrumented wheelchair ergometer, 3D motion analysis, and computerized open-circuit spirometry were used to collect joint kinetics and kinematics, handrim kinetics, propulsion temporal characteristics, and oxygen uptake pre- and posttraining during a submaximal exercise test to exhaustion. Each subject (n = 19) participated in a specific intervention program of supervised therapeutic exercise (strengthening, stretching, and aerobic exercise) for 6 weeks. Pre- and posttraining measurements were compared with the use of ANOVA with repeated measures. Significant training effects included increased exercise loads for all strengthening activities, decreased stroke frequency, increased maximum elbow extension angle, increased trunk and shoulder flexion/extension range of motion (ROM), increased handrim propulsive moment, increased wrist extension moment, and increased power output. Results suggest that this training program increased biomechanical economy (as defined by propulsive moment) without increasing shoulder or elbow joint stresses.