Adiponectin is an adipocyte-specific cytokine that has a protective role in the development of cardiovascular morbidities. As chronic kidney disease progresses, adiponectin levels increase and cardiovascular risk profiles change. Here we determined the association of baseline and longitudinal changes in adiponectin with different cardiovascular outcomes in 1255 type 2 diabetic hemodialysis patients in the German Diabetes and Dialysis Study. Within 4 years of follow-up, the hazard ratios to reach pre-specified, adjudicated end points were determined. The increased risk of cardiovascular events observed with high adiponectin levels at baseline was associated with high risks of sudden death and stroke but not of myocardial infarction. Adiponectin was negatively correlated with C-reactive protein and positively correlated with NT-pro-BNP, the latter significantly attenuating the associations with adverse outcome. Increased longitudinal levels of adiponectin during follow-up were associated with higher risks of adverse cardiovascular outcomes and death; associations weakened by a confounding effect of increased NT-pro-BNP. Our study suggests that high basal and increasing adiponectin levels in the dialysis population largely reflect a consequence of disease circumstances. Most likely, this rise is a counter-regulatory response to worsening health in keeping with adiponectin's potential to counteract inflammation.