We aimed to validate QUALEFFO-41 in Arabic language and to examine the use of QUALEFFO-41 in clinical practice for assessing quality of life in patients with vertebral fractures (VF). A total of 201 women were included in the study: 106 (53%) cases with at least one vertebral fracture which had been defined morphometrically and 95 (47%) women with OP or osteopenia and no fractures as a control group. The QUALEFFO was translated into Arabic and applied to case-control pairs with prevalent osteoporotic vertebral fractures to evaluate its reliability, validity, and discriminatory ability. It was also used to evaluate the quality of life (QOL) of case-control with prevalent morphometric fractures. The QOL of all subjects was concurrently assessed using SF-36 for comparison. QUALEFFO-41 had good reliability with adequate convergent and discriminatory validity. There were good correlations between QUALEFFO-41 and SF-36. Subjects with clinical osteoporotic vertebral fractures showed significant impairment of HRQoL on the QUALEFFO compared with controls. Similar results were also observed using the SF-36. ROC curve analysis revealed that QUALEFFO-41 had significant ability to discriminate between morphometric fracture subjects versus and controls. The QUALEFFO discriminates for pain (P = 0.002), physical function (P < 0.0001), social function (P = 0.04), general health (P = 0.001), and mental function (P = 0.01), whereas the SF-36 discriminates exclusively for physical function (P = 0.01) and social function (P = 0.02). The Moroccan Arabic version of the QUALEFFO is a reliable and valid instrument that can be administered to Arabic patients suffering from vertebral fracture osteoporosis to evaluate their quality of life. Its measurement properties were comparable with versions in other languages. In addition, the quality of life measured by QUALEFFO is decreased in patients with vertebral fracture due to OP.