OBJECTIVE The role of menopausal hormone therapy (HT) on vertebral fracture prevention after treatment discontinuation is controversial. The aim of this study was to assess the incidence of vertebral fracture in a group of women who received HT in early menopause compared with another group who did not receive such treatment after 20 years of follow-up. METHODS In 1990, we included 177 patients aged 43-57 years old (mean 49.1 ± 3.9 years) in a prospective study to evaluate the effect of different HT regimens on bone metabolism and mineral density. After 20-21 years, a total of 49 patients from the initial study were retrieved. These patients were divided into two groups: the first group included women who had taken HT, and those who constituted the control groups and had not taken HT formed the second group. Clinical and demographic data were analyzed and vertebral fracture was assessed by radiology using the Genant semiquantitative scale. RESULTS Of the 49 patients enrolled, 32 (65.3%) received HT for an average of 5.5 (± 2.96) years while the 17 (34.7%) remaining belonged to the control group without treatment. A higher rate of vertebral fracture was observed in the group receiving HT (p = 0.03). Depending on the degree of fracture (Genant semiquantitative method), subsequent analysis by subgroups corroborated the higher rate in the group receiving HT in all cases (p < 0.05). Multivariate analysis ruled out the effect of the clinical and demographic variables (current age, age at menopause, body mass index, type of menopause and drugs for the treatment of osteoporosis) in the final result. CONCLUSIONS In spite of the fact that this study does not have a large enough sample, our data suggest that HT used in the early years of menopause does not present a long-term protective effect on vertebral fracture after discontinuing treatment.