UNLABELLED: Our objective was to assess the association of self-reported non-persistence (stopping fracture-prevention medication for more than 1 month) and self-reported non-compliance (missing doses of prescribed medication) with perceived need for fracture-prevention medication, concerns regarding long-term harm from and/or dependence upon medications, and medication-use self-efficacy (confidence in one's ability to successfully take medication in the context of their daily life). INTRODUCTION: Non-persistence (stopping medication prematurely) and non-compliance (not taking medications at the prescribed times) with oral medications to prevent osteoporotic fractures is widespread and attenuates their fracture reduction benefit. METHODS: Cross-sectional survey and medical record review of 729 patients at a large multispecialty clinic in the United States prescribed an oral bisphosphonate between January 1, 2006 and March 31, 2007. RESULTS: Low perceived necessity for fracture-prevention medication was strongly associated with non-persistence independent of other predictors, but not with non-compliance. Concerns about medications were associated with non-persistence, but not with non-compliance. Low medication-use self-efficacy was associated with non-persistence and non-compliance. CONCLUSIONS: Non-persistence and non-compliance with oral bisphosphonate medication have different, albeit overlapping, sets of predictors. Low perceived necessity of fracture-prevention medication, high concerns about long-term safety of and dependence upon medication , and low medication-use self-efficacy all predict non-persistence with oral bisphosphonates, whereas low medication-use self-efficacy strongly predicts non-compliance with oral bisphosphonate medication. Assessment of and influence of these medication attitudes among patients at high risk of fracture are likely necessary to achieve better persistence and compliance with fracture-prevention therapies.