Background This two‐part study explored the safety, feasibility, and efficacy of a mild–moderate resistance isometric leg exercise program in ambulatory boys with Duchenne muscular dystrophy (DMD). Methods First, we used a dose escalation paradigm with varying intensity and frequency of leg isometric exercise to determine the dose response and safety in 10 boys. Second, we examined safety and feasibility of a 12‐wk in‐home, remotely supervised, mild–moderate intensity strengthening program in eight boys. Safety measures included T2 MRI, creatine kinase levels, and pain. Peak strength and function (time to ascend/descend four stairs) were also measured. Results Dose‐escalation revealed no signs of muscle damage. Seven of the eight boys completed the 12‐wk in‐home program with a compliance of 84.9%, no signs of muscle damage, and improvements in strength (knee extensors P < .01; knee flexors P < .05) and function (descending steps P < .05). Conclusions An in‐home, mild–moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory boys with DMD.

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