Increasing evidence suggests that high-intensity training (HIT) is a time-efficient exercise strategy to improve fitness. HIT has never been explored in neuromuscular diseases, likely because it may seem counterintuitive. A single session of high-intensity exercise has been studied without signs of muscle damage in facioscapulohumeral muscular dystrophy type 1 (FSHD1). We aimed to determine whether HIT is safe and effective in FSHD1 in a randomized, controlled parallel study. Untrained adults with genetically verified FSHD1 (n = 13) able to perform cycle-ergometer exercise were randomized to 8 weeks of supervised HIT (n = 6) (3 × 10-min cycle-ergometer-HIT/week) or 8 weeks of usual care (n = 7). Following this, all participants performed 8 weeks of unsupervised HIT (3 × 10-min cycle-ergometer-HIT/week). Primary outcome was fitness, maximal oxygen uptake/min/kg body weight. Furthermore, workload, 6-min walk distance, 5-time sit-to-stand time, muscle strength, and daily activity levels were measured. Pain, fatigue, and plasma-CK were monitored. Twelve patients completed the randomized part of the study. Plasma-CK levels and pain scores were unaffected by HIT. Supervised HIT improved fitness (3.3 ml O2/min/kg, CI 1.2-5.5, P < 0.01, n = 6, NNT = 1.4). Unsupervised HIT also improved fitness (2.0 ml O2/min/kg, CI 0.1-3.9, P = 0.04, n = 4). There was no training effect on other outcomes. Patients preferred HIT over strength and moderate-intensity aerobic training. It may seem counterintuitive to perform HIT in muscular dystrophies, but this RCT shows that regular HIT is safe, efficacious, and well liked by moderately affected patients with FSHD1, which suggests that HIT is a feasible method for rehabilitating patients with FSHD1.