Misalignments between powered exoskeleton joints and the user's anatomical joints are inevitable due to difficulty locating the anatomical joint axis, non-constant location of the anatomical joint axis, and soft-tissue deformations. Self-aligning mechanisms have been proposed to prevent spurious forces and torques on the user's limb due to misalignments. Several exoskeletons have been developed with self-aligning mechanisms based on theoretical models. However, there is no experimental evidence demonstrating the efficacy of self-aligning mechanisms in lower-limb exoskeletons. Here we show that a lightweight and compact self-aligning mechanism improves the user's comfort and performance while using a powered knee exoskeleton. Experiments were conducted with 14 able-bodied subjects with the self-aligning mechanism locked and unlocked. Our results demonstrate up to 15.3% increased comfort and 38% improved performance when the self-aligning mechanism was unlocked. Not surprisingly, the spurious forces and torques were reduced by up to 97% when the self-aligning mechanism was unlocked. This study demonstrates the efficacy of self-aligning mechanisms in improving comfort and performance for sit-to-stand and position tracking tasks with a powered knee exoskeleton.