To improve locomotor performance, coaches and clinicians encourage individuals with unilateral physical impairments to minimize biomechanical asymmetries. Yet, it is unknown if biomechanical asymmetries per se, affect metabolic energy expenditure in individuals with or without unilateral impairments during running. Thus, inter-leg biomechanical asymmetries may or may not influence distance-running performance. Purpose: We sought to determine whether running with asymmetric step times affects metabolic rate in unimpaired individuals. Methods: Ten unimpaired individuals were instructed to run on a force-measuring treadmill at 2.8 m/s and contact the ground simultaneously to the beat of an audible metronome. The metronome either played at time intervals equal to the respective participant’s preferred step times (0% asymmetry), or at time intervals that elicited asymmetric step times between legs (7, 14, and 21% step time asymmetry); stride time remained constant across all trials. We measured ground reaction forces and metabolic rates during each trial. Results: Every 10% increase in step time and stance average vertical ground reaction force asymmetry increased net metabolic power by 3.5%. Every 10% increase in ground contact time asymmetry increased net metabolic power by 7.8%. More asymmetric peak braking and peak propulsive ground reaction forces, leg stiffness, as well as positive and negative external mechanical work, but not peak vertical ground reaction force, increased net metabolic power during running. Step time asymmetry increases the net metabolic power of unimpaired individuals during running. Therefore, unimpaired individuals likely optimize distance-running performance by using symmetric step times and overall symmetric biomechanics.