Introduction Given the increasing incidence of medication-related jaw osteonecrosis, and recognition of the mucosal blood supply's importance, we have developed a non-invasive Real Time Optical Vascular Imaging (RTOVI) instrument. Imaging the red blood cells within the sub-mucosal capillary networks demonstrates the microcirculatory anatomy. We report a small trial, demonstrating the technique's viability, examining mucosal microcirculatory changes adjacent to osteonecrotic lesions.Aims Imaging the microvasculature of soft tissue margins of patients' exposed necrotic bone lesions in situ was intended to provide unique observational as well as quantitative data, using an image analysis routine, based on ImageJ software. Our interest was to evaluate whether this could offer valuable information for complex wound margin management.Methods Four osteoradionecrosis and four medication-related osteonecrosis patients (M:F 1:1 mean 68.25 years) were enrolled under the NRES Ethics 11/LON/0354 and KCL Research Ethics Committee (REC) BDM/14/15-14 approvals. Microvascular images from mucosal margins of exposed mandibular osteonecrosis lesions were compared with equivalent images from both uninvolved contralateral mucosa and similar mucosal sites in four healthy subjects.Results We demonstrated narrow hypo-vascularised oedematous lesion margins surrounded by a concentric inflammatory band and normal mucosa beyond. Parameters reporting individual capillary shape, via mean percentage of occupancy per capillary per field of view and capillary loop aspect ratio, differed significantly between groups (ANOVA, p = 0.0002 and p = 0.04 respectively). Values reporting capillary number and area showed expected changes but did not reach statistical significance.Conclusion This pilot study demonstrated the feasibility of mucosal microvascular imaging in assessing the microvascular changes found in the soft tissues at the margins of osteonecrotic lesions, with potential to inform therapeutic interventions and clinical decisions to continue or modify regime strategies at the earliest opportunity. Given the increasing incidence of medication-related jaw osteonecrosis, and the recognition of the importance of mucosal blood supply, we developed a non-invasive instrument demonstrating microcirculation anatomy by imaging transiting red blood cells.