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Background: To assess the cost-effectiveness of new treatments in Germany, the efficiency frontier (EF) method has been developed. We compared the cost-effectiveness analysis using international standards and the German methodology, using the heart failure drug sacubitril/valsartan as an example.Methods: A previously developed Markov model was adapted to include 4 treatment options: no treatment, enalapril, candesartan, and sacubitril/valsartan. The internationally used incremental cost-effectiveness ratio (ICER) was calculated, as well as cost-effectiveness acceptability curves. Additionally, EFs, net monetary benefits (NMBs), and price-acceptability curves were created according to German guidelines. All analyses were performed from the perspective of the German Statutory Health Insurance.Results: The base-case ICER for sacubitril/valsartan compared to enalapril is €19  300/quality-adjusted life-year. On the cost-effectiveness acceptability curve, sacubitril/valsartan is most likely to be cost-effective, out of all included comparators, from a hypothetical willingness-to-pay threshold of €18 250/quality-adjusted life-year onward. No EF could be constructed for the base case. Taking the uncertainty of the input parameters into account for the probabilistic sensitivity analysis, a NMB of around -€14 000 was calculated, depending on the outcome considered, with the NMB being zero at a daily price for sacubitril/valsartan ranging from €1.52 to €1.67.Conclusion: We calculated an ICER for Germany, comparable to previously published cost-effectiveness analyses for Europe, which widely concluded sacubitril/valsartan to be cost-effective. Using the German EF approach, a considerable discount needs to be applied before sacubitril/valsartan can be considered cost-effective. [ABSTRACT FROM AUTHOR]