OBJECTIVES: Chronic kidney disease is, increasingly, both a contributor to premature deaths and a financial burden to the health system, and is estimated to affect between 10% and 15% of the adult population in Western countries. Hypertension and, in particular diabetes, are significant contributors to the global burden of chronic kidney disease. Although it might increase costs, screening for, and improved management of, persons at increased risk of progressive kidney disease could improve health outcomes. We therefore sought to estimate the costs and health outcomes of alternative strategies to prevent end-stage kidney disease, compared with usual care. METHODS: A Markov model comparing: 1) intensive management versus usual care for patients with suboptimally managed diabetes and hypertension; and 2) screening for and intensive treatment of diabetes, hypertension, and proteinuria versus usual care was developed. Intervention effectiveness was based on published meta-analyses and randomized controlled trial data; costs were measured from a central health-care funder perspective in 2008 Australian dollars ($A), and outcomes were reported in quality-adjusted life-years (QALYs). RESULTS: Intensive treatment of inadequately controlled diabetes was both less costly (an average lifetime saving of $A133) and more effective (with an additional 0.075 QALYs per patients) than conventional management. Intensive management of hypertension had an incremental cost-effectiveness ratio (ICER) $A2588 per QALY gained. Treating all known diabetics with angiotensin-converting enzyme (ACE) inhibitors was both less costly (an average lifetime saving of $A825 per patient) and more effective than current treatment (resulting in 0.124 additional QALYs per patient). Primary care screening for 50- to 69-year-olds plus intensive treatment of diabetes had an ICER of $A13,781 per QALY gained. Primary care screening for hypertension (between ages 50 and 69 years) plus intensive blood pressure management had an ICER of $A491 per QALY gained. Primary care screening for proteinuria (between ages 50 and 69 years) combined with prescription of an ACE inhibitor for all persons showing proteinuria and all known diabetics had an ICER of $A4793 per QALY gained. CONCLUSIONS: Strategies combining primary care screening of 50- to 69-year-olds for proteinuria, diabetes, and hypertension followed by the routine use of ACE inhibitors, and optimal treatment of diabetes and hypertension, respectively, have the potential to reduce death and end-stage kidney disease and are likely to represent good value for money.