The mechanism underlying jaw osteoradionecrosis (ORN) is not fully understood, particularly in the early stages. To investigate bone and vessel pathogenesis in the early stages of jaw ORN, we generated a mandibular ORN model in miniature pigs (minipigs) by applying a combination of single-dose 25-Gy irradiation (IR) and tooth extraction. We studied 6 ORN model minipigs and 6 control, non-irradiated minipigs. We measured dynamic morphological changes, bone-remodeling-associated gene expression, sphingomyelinase activity, and local blood flow. Bone remodeling, including bone resorption and new bone formation, was observed within 15 days post-IR. Later, an ORN-related imbalance in bone metabolism gradually occurred, with loss of bone regeneration capacity, collagen collapse, and microvascular obliteration. Within 24 hrs post-IR, sphingomyelinase significantly increased in irradiated tissues. At 1 wk post-IR, local blood flow increased, but at 15 days post-IR, it significantly decreased to 50% below normal levels. This study provided details of the sequential occurrences in early-stage ORN in a large animal model. Our results suggested that reduced local blood flow and consequent hypovascularity may have caused an imbalance in bone remodeling. This suggested that microvessel damage may play a key role in the initiation of ORN.