This 7-year prospective observational study determined the predictors of re-fracture amongst 234 patients managed within a Secondary Fracture Prevention programme. Poor compliance, multiple co-morbidities, corticosteroid therapy, low hip bone mineral density (BMD) or low body weight were all significantly associated with re-fracture in patients commenced on long-term anti-resorptive therapy. Risk factors for osteoporotic fracture amongst treatment-na < ve patients are well established. In contrast, predictors of re-fracture in patients optimally managed within a Secondary Fracture Prevention (SFP) programme are ill-defined. This prospective observational study included 234 subjects with incident osteoporotic fractures managed long-term by the Concord SFP programme. Using Cox proportional hazards models, predictors of re-fracture were analysed separately for patients commenced on specific pharmacotherapy (group 1, N = 171) and subjects receiving calcium and/or vitamin D supplements only (group 2, N = 63). Relevant anthropometric, clinical and technical data were documented at each visit. Compliance and persistence were analysed as time-varying covariates. During a mean follow-up of 5.2 (range 3.5-7.3) years, 20.9 % of all subjects re-fractured (26.3 % in group 1, 6.3 % in group 2). Multivariate predictors of re-fracture in group 1 were significant co-morbidity (HR 2.04 if > 3, 95 % CI 1.10-3.79, p = 0.024), corticosteroid use (HR 1.75, 95 % CI 1.12-2.73, p = 0.013) and total hip BMD (HR 1.36 per 0.1 g/cm(2) decrease, 95 % CI 1.08-1.70, p = 0.008). In contrast, gender, prevalent fractures and lumbar spine BMD were not associated with re-fracture. Amongst patients with complete compliance data, a medication possession ratio of a parts per thousand currency sign 50 % (HR 3.36, 95 % CI 1.32-8.53, p = 0.011) and low body weight (HR 1.04 per 1-kg decrease, 95 % CI 1.003-1.08, p = 0.032) were significantly associated with re-fracture. Amongst patients managed within a dedicated SFP programme, poor compliance, multiple co-morbidities, corticosteroid therapy, low hip BMD or low body weight are all associated with increased risk of re-fracture. This subgroup of patients therefore require intensive management including strategies to improve compliance.