Adiponectin levels are increased in patients with type I diabetes especially in the presence of microangiopathy. Here we determined the predictive value of serum adiponectin levels and 8 adiponectin gene polymorphisms for mortality, cardiovascular events and end-stage renal disease in type I diabetic patients. This prospective, observational follow-up study of type I diabetics consisted of 438 patients with overt diabetic nephropathy that were compared to 440 type I patients with normal albumin excretion. These two groups were followed an average of 8 years and generally matched for gender, age and duration of diabetes. Cox regression analysis of 373 patients showed a covariate-adjusted hazard ratio for all-cause mortality of 1.46 for a change of one standard deviation in log10 of serum adiponectin. There was no association with cardiovascular events; however, serum adiponectin levels predicted end stage renal disease in a covariate-adjusted analysis. Two of eight gene polymorphisms, found in the 878 patients, were associated with increased serum adiponectin levels but none of the polymorphisms were associated with a renal or cardiovascular outcome. These studies show that high serum adiponectin levels predict mortality and progression to end stage renal disease in type I diabetic patients.