Up to 30% of patients relapse after orthognathic operations, and one reason might be incomplete neuromuscular adaptation of the masticatory muscles. Displacement of the mandible in sagittal or vertical directions, or both, leads to stretching or compression of these muscles. The aim of this study was to analyse stretching factors in 35 patients with retrognathism or prognathism of the mandible (Classes II and III). Tissue samples were taken from both sides of the masseter muscle (anterior and posterior) both before and 6 months after operation. Developmental myosin heavy chains MYH3 and MYH8, the fast and slow MYH 1, 2, and 7, and cyclo-oxygenase (COX) 2, forkhead transcription factor (FOX)O3a, calcineurin, and nuclear factor of activated T cells (NFAT)1c (stretching and regeneration-specific), were analysed by real time polymerase chain reaction (PCR). Correlations of Class II and III with sagittal and vertical cephalometric measurements ANB and ML-NL-angle were examined, and the results showed significant differences in amounts of MYH8 (p < 0.05), MYH1 (p < 0.05), and FOXO3a (p < 0.05) between the 2 groups. Regeneration factor COX2 is more dominant in Class II. Surgically, bite opening (ML/NL angle) correlated with stretching indicators FOXO3a, calcineurin, and NFAT1c only in Class II patients. This means that stretching of the masseter muscle caused by lengthening of the mandible and raising of the bite in Class II patients was more likely to lead to relapse (similar to that in patients with open bite) than in Class III patients. In conclusion, deep bite should be reduced more by incisor intrusion than by skeletal opening. The focus in these patients should be directed towards physiotherapeutic strengthening of the muscles of mastication, and more consideration should be given to change in the vertical dimension.