No previous studies have investigated the association between the bone material strength index (BMSi; an indicator of bone material properties obtained by microindentation) and the risk of incident fracture. The primary purpose of this prospective cohort study was to evaluate if BMSi is associated with incident osteoporotic fracture in older women, and secondarily, with prevalent fractures, anthropometric traits, or measurements of bone mineral density (BMD) by (dual-energy x-ray absorptiometry) DXA. In a population-based cohort, 647 women aged 75-80 years underwent bone microindentation using the OsteoProbe® device. Data on clinical risk factors (CRFs), prevalent fractures, and incident fractures were collected using questionnaires, medical records, and a regional x-ray archive. BMD and vertebral fracture assessment (VFA) were assessed by DXA (Hologic, Discovery A). Associations between BMSi, anthropometrics, BMD, and prevalent fractures were investigated using correlation and linear and logistic regression. Cox proportional hazards and competing risks analysis by Fine and Gray were used to study the association between BMSi and the risk of fracture and mortality. BMSi was weakly associated to age (r = -0.13, p < 0.001) and BMI (r = -0.21, p < 0.001), and to BMD of lumbar spine (β = 0.09, p = 0.02) and total hip (β = 0.08, p = 0.05), but only following adjustments. No significant associations were found between BMSi and prevalent fractures (self-reported and/or VFA identified, n = 332). During a median follow-up time of 6.0 years, 121 major osteoporotic fractures (MOF), 151 any fractures, and 50 deaths occurred. Increasing BMSi (per SD) was associated with increased risk of MOF (Hazard Ratio, HR = 1.29, 95% CI[1.07-1.56]), any fracture (HR = 1.29,[1.09-1.53]) and mortality (HR = 1.44, 95% CI[1.07-1.93]). The risk of fracture did not materially change with adjustment for confounders, CRFs, femoral neck BMD or when considering the competing risk of death. In conclusion, unexpectedly increasing BMSi was associated with greater fracture risk. The clinical relevance and potential mechanisms of this finding requires further study. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.