Soluble urokinase-type plasminogen activator receptor (suPAR) accumulates in patients with chronic kidney disease (CKD). In various non-CKD populations, suPAR has been proposed as a prognostic marker for mortality and cardiovascular disease. However, it is not known whether suPAR holds prognostic information in patients with mild-to-moderate CKD. In a prospective observational study of 476 patients with mild-to-moderate kidney disease, we examined multivariate associations between suPAR, overall mortality, and cardiovascular events. After a mean follow-up of 57 months, 52 patients died and 76 patients had at least one fatal or nonfatal cardiovascular event. Higher suPAR was directly and significantly associated with both overall mortality (univariate hazard ratio 5.35) and cardiovascular events (univariate hazard ratio 5.06). In multivariate analysis, suPAR remained significantly associated with cardiovascular events (full model, hazard ratio 3.05). Thus, in patients with mild-to-moderate CKD, suPAR concentrations show a clear, direct, and graded association with a higher risk for new-onset cardiovascular disease.Kidney International advance online publication, 4 June 2014; doi:10.1038/ki.2014.197.