OBJECTIVES: Health-related quality of life (HRQoL) might be one important patient reported endpoint (PRO) in determining the additional benefit of pharmaceuticals recently evaluated according to the newly established German law for reforming the market for pharmaceuticals (AMNOG). A comparative analysis is performed to gain insight how HRQoL was implemented in the benefit dossier by the pharmaceutical manufacturer on the one hand and how it was assessed in the benefit assessment by the Institute for Quality and Efficiency in Health Care (IQWiG) on the other hand. METHODS: We reviewed 23 published benefit dossiers and the corresponding benefit assessments, which the IQWiG performed since the implementation of the AMNOG in 2011. Corresponding statements concerning HRQoL in benefit dossiers and benefit assessment were faced narrative. RESULTS: Eighteen benefit dossiers reported HRQoL and a number of validated instruments were used, which were generally accepted by the IQWiG if not for major mistakes in the benefit dossiers (for example the use of another appropriate comparator). Overall, the pharmaceutical manufacturers have difficulties to clearly prove an additional benefit due to HRQoL because the used studies do not contain data on this endpoint or the results are statistical non-significant. The IQWiG draws a similar conclusion as the pharmaceutical manufacturers and attests none of the benefit dossiers an additional benefit due to HRQoL. A common methodological problem reported in the benefit assessments is for example a low response rate so that the data has high bias potential. CONCLUSIONS: None of the published benefit assessments state an additional benefit in HRQoL although this is an important PRO and the pharmaceutical manufacturers presented a range of accepted validated instruments to assess it. Dealing with data uncertainties concerning the HRQoL has to be accomplished in the future of the benefit assessment.