Duchenne Muscular Dystrophy (DMD) is characterized by progressive muscle weakness and wasting. Despite the sustained presence of satellite cells in their skeletal muscles, muscle regeneration in DMD patients seems inefficient and unable to compensate for the continuous muscle fiber loss. To find a molecular explanation, we compared the gene expression profiles of myoblasts from healthy individuals and DMD patients during activation and differentiation in culture. DMD cultures showed significant gene expression changes, even before dystrophin is expressed. We found a higher expression level of bone morphogenetic protein 4 (BMP4) in DMD cultures, which we demonstrate to inhibit differentiation into myotubes. In the later stages of differentiation, we observed a significant decline in expression of sarcomeric genes in the absence of dystrophin, probably contributing to sarcomeric instability. These results support the hypothesis that inefficient muscle regeneration is caused by impaired myoblast differentiation and impaired maintenance of the myotubes.