Results of the main Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial indicate that intensive glucose lowering increases cardiovascular and all-cause mortality. As the contribution of mild-to-moderate chronic kidney disease (CKD) to these risks is not known, we assessed the impact on cardiovascular outcomes in this population. Renal function data were available on 10,136 patients of the original ACCORD cohort. Of those, 6,506 were free of CKD at baseline and 3,636 met the criteria for CKD. Participants were randomly assigned to a treatment strategy of either intensive or standard glycemic goal. The primary outcome, all-cause and cardiovascular mortality, and prespecified secondary outcomes were evaluated. Risk for the primary outcome was 87% higher in patients with than in those without CKD (hazard ratio of 1.866; 95% CI: 1.651-2.110). All prespecified secondary outcomes were 1.5 to 3 times more frequent in patients with than in those without CKD. In patients with CKD, compared with standard therapy, intensive glucose lowering was significantly associated with both 31% higher all-cause mortality (1.306: 1.065-1.600) and 41% higher cardiovascular mortality (1.412: 1.052-1.892). No significant effects were found in patients without CKD. Thus, in high-risk patients with type II diabetes, mild and moderate CKD is associated with increased cardiovascular risk. Intensive glycemic control significantly increases the risk of cardiovascular and all-cause mortality in this population.Kidney International advance online publication, 17 September 2014; doi:10.1038/ki.2014.296.