The WHO Fracture Risk Assessment Tool (FRAX; http://www.shef.ac.uk/FRAX) estimates the 10-year probability of major osteoporotic fracture. Clodronate and bazedoxifene reduced nonvertebral and clinical fracture more effectively on a relative scale in women with higher FRAX scores. We used data from the Fracture Intervention Trial (FIT) to evaluate the interaction between FRAX score and treatment with alendronate. We combined the Clinical Fracture (CF) arm and Vertebral Fracture (VF) arm of FIT. The CF and VF arm of FIT randomized 4432 and 2027 women, respectively, to placebo or alendronate for 4 and 3 years, respectively. FRAX risk factors were assessed at baseline. FRAX scores were calculated by WHO. We used Poisson regression models to assess the interaction between alendronate and FRAX score on the risk of nonvertebral, clinical, major osteoporotic, and radiographic vertebral fractures. Overall, alendronate significantly reduced the risk of nonvertebral fracture (incidence rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.75–0.99), but the effect was greater for femoral neck (FN) bone mineral density (BMD) T-score ≤ −2.5 (IRR 0.76; 95% CI, 0.62–0.93) than for FN T-score > −2.5 (IRR 0.96; 95% CI, 0.80–1.16) (p = 0.02, interaction between alendronate and FN BMD). However, there was no evidence of an interaction between alendronate and FRAX score with FN BMD for risk of nonvertebral fracture (interaction p = 0.61). The absolute benefit of alendronate was greatest among women with highest FRAX scores. Results were similar for clinical fractures, major osteoporotic fractures, and radiographic vertebral fractures and whether or not FRAX scores included FN BMD. Among this cohort of women with low bone mass there was no significant interaction between FRAX score and alendronate for nonvertebral, clinical or major osteoporotic fractures, or radiographic vertebral fractures. These results suggest that the effect of alendronate on a relative scale does not vary by FRAX score. A randomized controlled trial testing the effect of antifracture agents among women with high FRAX score but without osteoporosis is warranted. © 2012 American Society for Bone and Mineral Research.