This study tested the hypothesis that skeletal muscles generate more mechanical energy in gait tasks that raise the center of mass compared to the mechanical energy they dissipate in gait tasks that lower the center of mass despite equivalent changes in total mechanical energy. Thirteen adults ran on a 10 degrees decline and incline surface at a constant average velocity. Three-dimensional (3D) joint powers were calculated from ground force and 3D kinematic data using inverse dynamics. Joint work was calculated from the power curves and assumed to be due to skeletal muscle-tendon actuators. External work was calculated from the kinematics of the pelvis through the gait cycle. Incline vs. decline running was characterized with smaller ground forces that operated over longer lever arms causing larger joint torques and work from these torques. Total lower extremity joint work was 28% greater in incline vs. decline running (1.32 vs. -1.03J/kgm, p<0.001). Total lower extremity joint work comprised 86% and 71% of the total external work in incline (1.53J/kgm) and decline running (-1.45J/kgm), which themselves were not significantly different (p<0.180). We conjectured that the larger ground forces in decline vs. incline running caused larger accelerations of all body tissues and initiated a greater energy-dissipating response in these tissues compared to their response in incline running. The runners actively lowered themselves less during decline stance and descended farther as projectiles than they lifted themselves during incline stance and ascended as projectiles. These data indicated that despite larger ground forces in decline running, the reduced displacement during downhill stance phases limited the work done by muscle contraction in decline compared to incline running.