Vertebral fractures are a common complication of osteoporosis and may cause a decrease of health-related quality of life (HRQOL). This study was designed to determine the impact of incident vertebral fractures on HRQOL. The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double blind trial, in which women were taking raloxifene or placebo. This study was done in European centers only in a subset of 361 women from seven European countries, all with prevalent vertebral fractures. A specific questionnaire for osteoporosis developed by the International Osteoporosis Foundation was used for assessment at baseline, 1, 2 and 3 years. This questionnaire, Qualeffo, contains 41 questions in the domains pain, physical function, social function, general health perception and mental function. Domain and total scores are expressed on a 100-point scale with 0 corresponding to the best HRQOL. Standardized lateral spinal radiographs were made at baseline, 2 and 3 years and evaluated in a central facility. Sixty-seven patients sustained a fracture in a vertebra that was not fractured at baseline (incident vertebral fractures). Twenty of these were accompanied by signs and symptoms necessitating immediate doctor's attention (clinical vertebral fractures) and 47 vertebral fractures were only diagnosed on radiographs (subclinical vertebral fractures). Incident vertebral fractures (clinical and subclinical) were associated with an increase of back pain (mean score change 6.4; 95% CI 2.1-10.7), deterioration of physical function (mean score change 2.4; 95% CI 0.1-4.8), and worse general health perception (mean score change 3.8; 95% CI 0.1-7.5). Score changes for patients with subclinical vertebral fractures were intermediate between those for patients with clinical vertebral fractures and patients without incident vertebral fracture. Clinical and subclinical incident vertebral fractures both have an adverse impact on HRQOL. © International Osteoporosis Foundation and National Osteoporosis Foundation 2004.