While current use of menopausal hormone therapy (MHT) reduces the risk of osteoporotic fractures, epidemiologic studies suggest that protection wears off rapidly after discontinuation of treatment. The authors identified 5,589 first osteoporotic fractures (2,235 major osteoporotic fractures) among 70,182 postmenopausal women from the French E3N cohort (1992-2008) and used Cox multivariate proportional hazards regression models to estimate hazard ratios. Persistence of protection against major osteoporotic fractures after MHT discontinuation was only observed when MHT had been used for at least 5 years, with a slightly more important decrease within the 5 years after discontinuation (compared with never use of MHT, hazard ratio = 0.68, 95% confidence interval: 0.50, 0.92) than beyond 5 years (hazard ratio = 0.83, 95% confidence interval: 0.69, 0.99); the P value for homogeneity between the 2 estimates was not significant. Oral estrogen use and transdermal estrogen use conveyed similar estimates in past users. Among current users, the authors confirmed a protective effect of MHT against risk of osteoporotic fractures. These findings, which relied on a number of MHT combinations, suggested that such therapies should be used for 5 years or more for reducing risk of fracture after treatment discontinuation.