Background: It has long been thought by many baseball coaches and players that throwing the fastball from the stretch is more stressful to the shoulder and elbow than throwing the fastball from the wind-up. However, no research has compared the biomechanics of these 2 pitch variations. Hypothesis: There are differences in shoulder and elbow kinetics, kinematic position at front-foot contact, timing, and ball velocity between the 2 pitching variations. Study Design: Controlled laboratory study. Methods: Twenty-eight professional baseball pitchers (aged 22.1 ± 2.8 years) pitched fastballs from both the wind-up and stretch positions in an indoor laboratory setting. Three-dimensional motion-analysis systems were employed to capture the pitching motion. Kinetic variables, kinematic variables at lead-foot contact, and temporal variables of the 2 pitching variations were compared. Results: There was no significant difference between the 2 pitch variations for the kinetic, kinematic, or temporal variables. The difference between the ball velocities was statistically significant, but the mean difference was only 0.2 m/s. Conclusions: The pitching biomechanics between the wind-up and stretch fastball showed no statistical differences in joint kinetics, kinematics, or timing, and clinically insignificant differences in ball velocity. Clinical Relevance: The current results suggest that pitching the fastball from the stretch is not necessarily more stressful to the shoulder and elbow. © 2008 American Orthopaedic Society for Sports Medicine.