OBJECTIVES: To validate a theoretical method, using a case study of efficiency frontier analysis for HIV/AIDS prevention and treatment, for quantifying lower and upper limits of the ICER configurated as a slope of the connected lines on the efficiency frontier, whose research poster in theory was presented at the ISPOR Dublin 2007. METHODS: A validation study was conducted based on the evidence published on the Journal of Medical Economics as one of the first studies that identified cost-effectiveness variation in efficient frontiers for HIV/AIDS prevention and treatment documented in the database, Cost-Effectiveness Analysis Registry, at Tufts Medical Center in 2002-2007. RESULTS: Recognizing that there are two types of efficiency frontier represented with a monotonically increasing function of QALY on the Y-axis and Cost on the X-axis, and also each efficiency frontier is formulated by two regression models: log and square-root models, two types of the mathematical formulae of derivatives were obtained according to each regression model. The formula of derivatives can provide the slope of the tangent on the efficiency frontier curve, given an arbitrary value of cost (or QALY). Therefore, we developed the formula that can provide lower and upper slopes of the two tangents, given an arbitrary ICER slope which is represented by connecting two points on the efficiency frontier curve. The examples of calculations conducted were graphically illustrated according to each regression model. CONCLUSIONS: Through this validation study, we can confirm that an application of our method is theoretically and practically feasible to estimate the lower and upper limits of an ICER arbitrarily given on the efficiency frontier curve. This approach will provide us with more useful information on the question how we could interpret and justify the high value of ICER of new technologies such as molecular-targeted drugs.