When choosing from a menu of treatment alternatives, the optimal treatment depends on the objective function and the assumptions of the model. The classical decision rule of cost-effectiveness analysis may be formulated via two different objective functions: (i) maximising health outcomes subject to the budget constraint or (ii) maximising the net benefit of the intervention with the budget being determined ex post. We suggest a more general objective function of (iii) maximising return on investment from available resources with consideration of health and non-health investments. The return on investment approach allows to adjust the analysis for the benefits forgone by alternative non-health investments from a societal or subsocietal perspective. We show that in the presence of positive returns on non-health investments the decision-maker's willingness to pay per unit of effect for a treatment program needs to be higher than its incremental cost-effectiveness ratio to be considered cost-effective.