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BACKGROUND Data have pointed at an impaired fracture healing with fluoroquinolones and thus potentially a decreased bone biomechanical competence. OBJECTIVES To study fracture risk associated with antibiotics. METHODS It is a case control study. There were 124,655 fracture cases and 373,962 age and gender matched controls. The main exposure was use of various groups of antibiotics. Confounder control was performed for social variables, contacts to hospitals and general practitioners, alcoholism and a number of other variables. RESULTS An increased risk of any fracture (OR =1.45, 95% CI: 1.42 -1.49), hip (1.46, 95% CI: 1.35- 1.58), forearm (1.67, 95% CI: 1.55 -1.80), and spine fractures (1.38, 95% CI: 1.18-1.60) was seen with the use of dicloxacillin and flucloxacillin. There was a dose response relationship for overall risk of fractures, hip, and forearm fractures but not for spine fractures with dicloxacillin and flucloxacillin. None of the other groups of antibiotics against bacteria, tuberculosis, virus, and fungi were systematically associated with any major change in the risk of fractures. CONCLUSION Dicloxacillin and flucloxacillin seem associated with an increased risk of fractures. The cause for this increase has to be determined but may be related to their use against infections of the bone, the increase thus rather being due to the underlying disease than the drug. Other types of antibiotics especially the fluoroquinolones were not systematically associated with an increased risk of fractures.