OBJECTIVES: To estimate the influence of non-compliance on the risk of fractures in German osteoporosis patients treated with oral bisphosphonate (oBP) therapy. METHODS: IMS® Disease Analyzer database was used; includes 11 million patients from office-based physicians. Eligible osteoporosis patients (excluding malignant diseases, any anticancer or cytostatic hormone prescription, Paget’s disease or AIDS) had data available ≥1-year before and after initiating oBP treatment (December 2004-November 2007). Compliance was measured as Medical Possession Ratio (MPR; prescribed to assumed number of therapy units). MPR >80% assumed compliance. MPR was calculated for patients on therapy up to 2 years. Fractures were identified by ICD-10 codes; only fractures 3 months after initiating oBP were included. The influence of compliance on time to fracture was determined by Kaplan-Meier and Cox regression analyses. The model was adjusted for gender, age, prevalence of fractures 1 year before index prescription, calcium/vitamin D co-prescription, continuation of the initial regimen after 6 months and after 1 year.   RESULTS: A total of 4738 patients’ data were analyzed: 1365 (28.8%) with previous fractures. The total number of patients receiving oBP treatment was 177 (3.7%) daily, 4367 (92.2%) weekly and 194 (4.1%) monthly. After 2 years, 14.5% (daily), 12.2% (weekly), and 9.7% (monthly) of patients experienced a fracture. The time to fracture was significantly longer for compliant versus non-compliant patients (log rank test; p=0.013).  Compliance was associated with a 26% (95% CI 10–39%) decrease in the fracture rate versus non-compliance. Higher age (>60 years) (44% increase; 95%CI 3-100%) and previous fractures (29% increase; 95%CI 5-57%) were associated with a significantly higher risk of fractures. CONCLUSIONS: Patients receiving oBP therapy who are compliant have a decreased risk of fractures versus non-compliant patients. Older patients and those with fracture history are particularly at risk of fracture. These findings highlight the need to improve compliance to reduce the risk of osteoporosis-associated fractures.