Runners often reduce their pace during inclined running to maintain a constant metabolic workload, known as iso-efficiency speed (a speed-incline combination with the same metabolic intensity as level running). This study investigates changes in lower extremity (LE) joint work profiles when running on an incline at iso-efficiency speed. Eleven collegiate distance runners completed a treadmill running task under three conditions (0%, 4%, and 8% incline). Running velocity was reduced with increasing incline to ensure a consistent metabolic workload across conditions. An 8-camera motion capture system and an instrumented treadmill collected kinematics and ground reaction forces. Visual 3D was used to calculate ankle, knee, and hip joint powers, while custom software (MATLAB) calculated ankle, knee, and hip joint positive and negative work values. A significant increase in LE total positive work was attributed to greater ankle and hip joint positive work with steeper inclines. Reduced LE total negative work resulted from lower knee and hip joint negative work as incline increased. Results suggest that at iso-efficiency speeds, inclined treadmill running increases eccentric demands on the ankle joint and concentric demands on the ankle and hip joints, benefiting training programmes to optimize cardiorespiratory stimuli while reducing mechanical demand on specific extremity structures.