OBJECTIVE: Develop methodology to create a more globally informative, CE-based "valuation" that is useful in comparing interventions across diseases. METHODS: Cost effectiveness ratios (CERs), presenting the financial cost per quality-adjusted life year saved, enable decision makers to assess the value of health care products/services in reducing misery as well as extending life. Although CERs are valuable especially in comparing options for a given disease, decision makers have struggled in using them to compare the value of alternatives across diseases. For example, Garvey (2000) noted that the CER use of sildenafil in erectile dysfunction was favorable compared with treatments in other diseases, such as renal dialysis and coronary artery-bypass graft surgery in current literature. Garvey concluded that while the CER comparisons were valid on the "local" (condition-specific) comparisons, they are problematic in "global" comparison across diseases. This could be attributed to the failure of CER to account for different degrees of medical necessity, baseline utility, public health importance, and other relevant issues. Manifold theory helps address the issues arising from global versus local properties from a geometric perspective. Manifold theory provides an excellent mathematical model to develop a global, cost-effective based valuation of interventions that can incorporate dimensions, such as medical necessity while preserving the local functionality of useful condition-specific CER comparisons. RESULTS: Examples of two different manifolds derived under different assumptions are presented. The development of the first manifold is derived via theoretical criteria for rational health resource allocation, while the second manifold is based on empirical data that infer "rules at work" in the decision-making coverage for the U.S. Medicare system. Calculations of global valuations for renal dialysis, cholesterol-lowering medication and coronary artery bypass graft surgery are presented and compared to that of sildenafil. CONCLUSIONS: The resultant values, presented side-by-side with published CER's present a more globally interpretable "valuation".