Objectives: The aim of this study was to assess the microarchitecture and turnover in irradiated cancellous mandibular bone and the relation with radiation dose, to elucidate the effects of radiotherapy on the mandible. Patients and methods: Mandibular cancellous bone biopsies were taken from irradiated patients and controls. Micro-CT scanning was performed to analyze microstructural bone parameters. Bone turnover was assessed by histomorphometry. Local radiation dose at the biopsy site (Dmax) was estimated from radiotherapy plans. Results: Twenty-seven irradiated patients and 35 controls were included. Osteoid volume (Osteoid Volume/Bone Volume, OV/BV) [0.066/0.168 (median/interquartile range (IQR), OV/BV; %), P < 0.001], osteoid surface (Osteoid Surface/Bone Surface, OS/BS) [0.772/2.17 (median/IQR, OS/BS; %), P < 0.001] and osteoclasts number (Osteoclasts per millimetre bone surface, Ocl/mmBS; mm2) [0.026/0.123 (median/IQR, Ocl/mmBS; mm2), P < 0.001] were decreased; trabecular number (Tb.N) was lower [1.63/0.63 (median/IQR, Tb.N; 1/mm−1), P = 0.012] and trabecular separation (Tb.Sp) [0.626/0.24 (median/IQR, Tb.Sp; μm), P = 0.038] was higher in irradiated mandibular bone. With higher Dmax, trabecular number increases (Spearman's correlation R = 0.470, P = 0.018) and trabecular separation decreases (Spearman's correlation R = −0.526, P = 0.007). Bone mineral density (BMD, milligrams hydroxyappetite per cubic centimetre, mgHA/cm3) [1016/99 (median/IQR, BMD; mgHA/cm3), P = 0.03] and trabecular separation [0.739/0.21 (median/IQR, Tb.Sp; μm), P = 0.005] are higher whereas connectivity density (Conn Dens) [3.94/6.71 (median/IQR, Conn Dens), P = 0.047] and trabecular number [1.48/0.44 (median/IQR, Tb.N; 1/mm−1), P = 0.002] are lower in Dmax ≤50 Gy compared to controls. Conclusions: Radiotherapy dramatically impairs bone turnover in the mandible. Deterioration in microarchitecture only affects bone irradiated with a Dmax of <50 Gy. The 50 Gy value seems to be a critical threshold to where the effects of the radiation is more detrimental.