Background: low–moderate intensity strength training to failure increases strength and muscle hypertrophy in healthy people. However, no study assessed the safety and neuromuscular response of training to failure in people with severe haemophilia (PWH). The purpose of the study was to analyse neuromuscular responses, fear of movement, and possible adverse effects in PWH, after knee extensions to failure. Methods: twelve severe PWH in prophylactic treatment performed knee extensions until failure at an intensity of five on the Borg CR10 scale. Normalised values of amplitude (nRMS) and neuromuscular fatigue were determined using surface electromyography for the rectus femoris, vastus medialis, and vastus lateralis. After the exercise, participants were asked about their perceived change in fear of movement, and to report any possible adverse effects. Results: Patients reported no adverse effects or increased fear. The nRMS was maximal for all the muscles before failure, the median frequency decreased, and wavelet index increased during the repetitions. The vastus lateralis demonstrated a higher maximum nRMS threshold and earlier fatigue, albeit with a lower and more progressive overall fatigue. Conclusions: severe PWH with adequate prophylactic treatment can perform knee extensions to task failure using a moderate intensity, without increasing fear of movement, or adverse effects.