OBJECTIVES: In Germany, an early assessment of benefit (EAB) is required for new medicines since January 2011. The pharmaceutical manufacturer submits a dossier on additional benefit over comparative treatment which is subsequently evaluated by the Institute for Quality and Efficiency in Health Care (IQWiG). Stakeholders can comment on the evaluation in a formal comments procedure. The final decision on additional benefit is made by the Federal Joint Committee (G-BA); it provides the basis for price negotiations between manufacturer and statutory health insurance funds. Quality of life (QoL) is one of four criteria for benefit evaluation. This qualitative study aimed to determine methodological requirements for QoL measurement in the German EAB. METHODS: A qualitative content analysis according to Mayring was conducted. Documents of all EABs completed until December 2013 (including dossier, IQWiG evaluation, protocol of the oral hearing, and G-BA decision) were searched for the term QoL or synonyms. Relevant passages were extracted and reduced to key content by two researchers independently. On the basis of subsequent consensus building, recurring themes of the term’s usage in the EAB process were identified. RESULTS: In the 66 early assessments of benefit included in the analysis, a range of methodological requirements regarding QoL assessment, analysis, and interpretation emerged. Dominant topics included: the appropriate level of disease-specificity of QoL instruments; required evidence on an instrument's validity and on the validity of a minimal important difference; appropriate duration of QoL assessment; consequences of potential bias due to unblinded study design or missing data; interpretation of results that differed between subscales of an instrument; non-acceptance of surrogate endpoints for QoL. CONCLUSIONS: Evidence on QoL can have high impact on the additional benefit determined by the G-BA. Therefore, QoL assessment and analysis in clinical studies that shall enter benefit dossiers should confirm with a range of methodological requirements.