In the mid-1970s, an unusual chronic kidney disease of multifactorial origin (CKDmfo), also known as CKD of unknown aetiology (CKDu), began to manifest in several economically poor, tropical, agricultural countries. This preventable, environmentally induced, occupational disease affects several peri-equatorial countries; it first manifested in Sri Lanka in the mid-1990s. The study goal was to estimate the costs of eradicating CKDmfo and the resulting cost savings, using CKDmfo in Sri Lanka as an example. This chronic disease model is applicable to CKDu and few other chronic diseases in other countries.Eight cost-effective, key interventions were identified that are essential to eradicate CKDmfo. A systematic assessment was performed on these interventions (including providing clean water, behavioural and lifestyle changes, alleviating malnutrition, reducing irresponsible and overuse of agrochemicals, and cost-effective treatment options), the cost of prevention, and the resultant cost savings. A cost-benefit analysis was based on the data collected during the past 20 years of work in Sri Lanka.The yearly cost required to eradicate the disease was approximately one-tenth of the current annual operating and opportunity costs due to CKDmfo. Analysis indicates that implementation of a focussed chronic disease-prevention plan using essential multiple interventions, CKDmfo can be eradicated within 15 years. This includes provision of potable water; real-time disease surveillance program; public and professional education; prevention of environmental pollution; alleviation of poverty and associated malnutrition; sustainable self-sufficiency in food, clean water, energy, and security; diversification of economy and job opportunities; sustainable economic development; regionwide programs of effective screening, early diagnosis and intervention to reverse the disease progression at earliest possible; and effective treatment of CKDmfo.This analysis is based on multiple population-level, chronic disease-eradication strategies that include an interdisciplinary, geographic information system (GIS)-based, regionwide, long-term research and intervention program; economic diversification; and environmental, socioeconomic, and behavioural improvements. Such an approach will facilitate identification of root causes and key risk factors, enabling implementation of cost-effective longer-term interventions to eradicate chronic diseases, applicable to other countries as well.