To investigate the pathogenesis and sequelae of symptomatic vertebral fractures (VF) in men, we have performed a case-control study, comparing 91 men with VF (median age 64 years, range 27-79 years) with 91 age-matched control subjects. Medical history, clinical examination and investigations were performed in all patients and control subjects, to identify potential causes of secondary osteoporosis, together with bone mineral density (BMD) measurements. BMD was lower at the lumbar spine and all sites in the hip in patients with VF than in control subjects (p < 0.001). Potential underlying causes of secondary osteoporosis were found in 41% of men with VF, compared with 9% of control subjects (OR 7.1; 95% CI 3.1-16.4). Oral corticosteroid and anti-convulsant treatment were both associated with a significantly increased risk of VF (OR 6.1; 95% CI 1.3-28.4). Although hypogonadism was not associated with an increased risk of fracture, the level of sex hormone binding globulin was higher (p < 0.001) and the free androgen index lower (p < 0.001) in men with VF than control subjects. Other factors associated with a significantly increased risk of VF were family history of bone disease (OR 6.1; 95% CI 1.3-28.4), current smoking (OR 2.8; 95% CI 1.2-6.7) and alcohol consumption of more than 250 g/week (OR 3.8; 95% CI 1.7-8.7). Men with VF were more likely to complain of back pain (p < 0.001) and greater loss of height (p < 0.001) than control subjects, and had poorer (p < 0.001) scores for the energy, pain, emotion, sleep and physical mobility domains of the Nottingham Health Profile. We conclude that symptomatic VF in men are associated with reduced BMD, underlying causes of secondary osteoporosis such as corticosteroid and anti-convulsant treatment, family history of bone disease, current smoking and high alcohol consumption, and that they impair the perceived health of the individual.