PURPOSE: Markers of micro- and macrovascular disease are needed in type 1 diabetes in order to identify patients at risk of severe complications. Osteoprotegerin (OPG) is expressed in vascular myocytes, and increasing levels have been reported in type 1 diabetes. Consequently, we investigated OPG as a non-invasive marker of micro- and macrovascular complications in long-term type 1 diabetic patients. METHODS: This was a cross-sectional study of 200 type 1 diabetic patients with long diabetes duration from a population-based cohort from Fyn County, Denmark. Patients were examined in 2007-2008, and OPG was measured and correlated to diabetes-associated complications: retinopathy, nephropathy, neuropathy and macrovascular disease. RESULTS: Median age and duration of diabetes was 58.7 years (range 37.7-84.4 years) and 43 years (range 34-70 years), respectively. Median level of OPG was 1257 pg/ml (range 379-5706 pg/ml). In univariate analyses, OPG was related to age, duration of diabetes, female gender, nephropathy and inversely to diastolic blood pressure. In an age- and sex-adjusted model, higher levels of OPG were associated with a higher risk of nephropathy (OR 2.54, 95% confidence interval 1.09-5.90 for third vs. first tertile). Statistical significance was, however, lost in a multivariate model, and proliferative diabetic retinopathy, neuropathy and macrovascular disease was not associated with OPG in either model. CONCLUSIONS: Some associations of OPG and nephropathy were found in a long-term type 1 diabetic cohort. Prospective studies are needed in order to determine whether OPG can be used to predict nephropathy.