Hip fracture risk is usually evaluated using dual energy X-ray absorptiometry (DXA) or quantitative computed tomography (QCT) which provide surrogate measures for proximal femoral strength. However, proximal femoral strength can best be estimated explicitly by combining QCT with finite element (FE) analysis. To evaluate this technique for predicting hip fracture in older men and women, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) QCT scans of 5500 subjects were obtained. During 4-7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as age- and sex-matched controls. FE-strength of the left hip of each subject for stance (F(Stance)) and posterolateral fall (F(Fall)) loading, and total femur areal bone mineral density (aBMD) were computed from the QCT data. F(Stance) and F(Fall) in incident hip fracture subjects were 13%-25% less than in control subjects (p = 0.006) after controlling for demographic parameters. The difference between FE strengths of fracture and control subjects was disproportionately greater in men (stance, 22%; fall, 25%) than in women (stance, 13%; fall, 18%) (p = 0.033), considering that F(Stance) and F(Fall) in fracture subjects were greater in men than in women (p