In the Fracture Intervention Trial (FIT) Long Term Extension (FLEX) Trial, 10 years of alendronate (ALN) did not significantly reduce the risk of nonvertebral fractures (NVFs) compared with 5 years of ALN. Continuing ALN reduced the risk of clinical but not morphometric vertebral fractures regardless of baseline vertebral fracture status. In previous studies, ALN efficacy for NVF prevention in women without prevalent vertebral fracture was limited to those with femoral neck (FN) T-scores of -2.5 or less. To determine whether the effect of long-term ALN on fracture differs by vertebral fracture status and femoral neck (FN) T-score, we performed a post hoc analysis using FLEX data, a randomized, double-blind, placebo-controlled trial among 1099 postmenopausal women originally randomized to ALN in the FIT with mean ALN use of 5 years. In the FLEX Trial, women were randomized to placebo (40%) or ALN 5 mg/day (30%) or ALN 10 mg/day (30%) for an additional 5 years. Among women without vertebral fracture at FLEX baseline (n = 720), continuation of ALN reduced NVF in women with FLEX baseline FN T-scores of -2.5 or less [relative risk (RR) = 0.50, 95% confidence interval (CI) 0.26-0.96] but not with T-scores of greater than -2.5 and -2 or less (RR 0.79, 95% CI 0.37-1.66) or with T-scores of greater than -2 (RR 1.41, 95% CI 0.75-2.66; p for interaction = .019). Continuing ALN for 10 years instead of stopping after 5 years reduces NVF risk in women without prevalent vertebral fracture whose FN T-scores, achieved after 5 years of ALN, are -2.5 or less but does not reduce risk of NVF in women whose T-scores are greater than -2.