Vertebral fractures are the hallmark of osteoporosis, responsible for increased back pain, impairment of mobility and functional limitations. These factors have an impact on patients' health-related quality of life (QOL). The aim of this study was to assess QOL, using QUALEFFO, in osteoporotic postmenopausal women, according to the number and the severity of the vertebral fractures. A group of 629 osteoporotic postmenopausal women (60-80 years) with symptoms that, according to a rheumatologist, could be related to a vertebral fracture, had spine X-rays with standardized procedures. All the X-rays were assessed in a central facility. The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical function (P=0.001), social function (P=0.002) and total score (P=0.027). Patients with higher grades of vertebral deformities, i.e., more severe fractures, had low QOL in these three domains, too (P<0.0001, P<0.0001 and P=0.005, respectively). There was no difference in QOL according to the thoracic or lumbar location of the fractures. Both anterior and middle deformities of the vertebral bodies had a negative impact on QOL. In none of the analyses were the pain and mental function domains of QUALEFFO discriminant among the patients. QOL, assessed by an osteoporosis-specific instrument, is decreased in osteoporotic women as a function of both the number and the severity of the vertebral fractures. Treating women with prevalent fractures may avoid a further decrease in their quality of life.