OBJECTIVES: Early benefit assessment in Germany under the AMNOG legislation requires a direct comparison with the appropriate comparator determined by the Federal Joint Committee (G-BA). In case no head-to-head studies are available, submission of indirect comparisons is permitted to assess the additional benefit of the new drug. The aim of this study was to comprehensively analyze the submissions of indirect comparisons reviewed so far by the Institute for Quality and Efficiency in Health Care (IQWiG) from January 2011 until May 2013. METHODS: A systematic review of all 48 published assessment reports was performed. RESULTS: There is a mismatch between the original intention of the early benefit assessment and its actual outcome. Until May 2013, 14 indirect comparisons have been conducted and submitted by manufacturers regarding the early benefit assessment. Only one indirect comparison has been accepted in a subindication by the IQWiG. However the results did not cause an added value of the drug in this respective application. In seven cases the indirect comparison was declined due to a different comparator as determined by the G‑BA. Three indirect comparisons were declined because of methodological deficiencies and another three indirect comparisons were declined because non-adjusted indirect comparisons were performed. CONCLUSIONS: The IQWiG only accepts adjusted indirect comparisons. The application of the correct methodology is necessary to gain valid results and shall not be questioned. The IQWiG approach is accurate with regard to contents and correct in a legal sense. However the procedure shows, that the external preconditions and methodological requirements are demanding and almost impossible to fulfill. Main reason for denial is the divergence from the prespecified appropriate comparator set by the G-BA. To get back to the original aim of the early benefit assessment, a more realistic and reasonable determination of the appropriate comparator would be desirable.