Muscle fatigue is considered as a risk factor for developing playing-related muscular disorders among professional pianists and could affect musical performance. This study investigated in 50 pianists the effect of fatiguing repetitive piano sequences on the development of forearm muscle fatigue and on piano performance parameters. Results showed signs of myoelectric manifestation of fatigue in the 42-electromyographic bipolar electrodes positioned on the forearm to record finger and wrist flexor and extensor muscles, through a significant non-constant decrease of instantaneous median frequency during two repetitive Digital (right-hand 16-tones sequence) and Chord (right-hand chords sequence) excerpts, with extensor muscles showing greater signs of fatigue than flexor muscles. In addition, muscle fatigue negatively affected key velocity, a central feature of piano sound intensity, in both Digital and Chord excerpts, and note-events, a fundamental aspect of musicians' performance parameter, in the Chord excerpt only. This result highlights that muscle fatigue may alter differently pianists' musical performance according to the characteristics of the piece played.